2009 - Institut Pasteur de Lille

Transcription

Public Health and
Molecular Epidemiology
of Aging-Related
Diseases
Inserm U 744
Institut Pasteur de Lille
University Lille Nord de France
affilated to IFR 142
Philippe AMOUYEL
Contact :
00 33 3 20 87 77 10 / 77 62
[email protected]
Group members common facilities :
Fiévet-Verrecas Nathalie, Engineer IPL
Marécaux Nadine, Engineer IPL
Codron Valérie, Technician IPL
Desmoucron Patricia, Technician IPL
Grupposo Marie-Catherine, Technician Inserm
Hermant Xavier, Technician IPL
Delbart Anne-Sophie, Administrative staff IPL
Peingnez Sabine, Administrative staff IPL
Steclebout Chantal, Administrative Staff IPL
Lombart Béatrice, Technician IPL
107
Research Report 2008/2009
Contents
Cardiovascular, Metabolic and Neurodegenerative Diseases
3 Teams
• Public health and epidemiology of vascular diseases
Philippe AMOUYEL
Contact : 00 33 3 20 87 77 10 / 77 62 - [email protected]
• Search for the molecular determinants of cardiovascular diseases
via proteomic analysis and candidate gene approaches
Florence PINET
Contact : 00 33 3 20 87 72 15 - fl[email protected]
• Search for the molecular determinants of neurodegenerative diseases
via transcriptomic anc candidate gene approaches
Jean-Charles LAMBERT
Contact : 00 33 3 20 87 73 91 - [email protected]
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Contents
related to ageing in humans. Two major fields have been
studied : cardiovascular diseases and neurodegenerative diseases.
- This knowledge will enable us to suggest and develop
new strategies for the prevention and treatment of
these diseases.
A - Research Report
1 - Summary
Our objective consists in the gain of knowledge on the impact
of the environmental and genetic determinants in the
occurence, the evolution and the prevention and treatment
of two pathologies related to ageing : cardiovascular and
neurodegenerative diseases. The integration within the unit
of an epidemiological know-how and the control biology tools
(high throughput genomics, transcriptomics, proteomics,
bioinformatics) adjusted to the epidemiological approach,
allowed us to carry out this program.
One of the main specificities of this unit is the integration in
the same laboratory of various types of scientific and medical
know-how, from expertise in epidemiological methods and
clinical research to the use of analytical techniques
(genomics, transcriptomics, proteomics, bio-computing, cell
biology) to address certain functional aspects of
determinants identified.
Studies which have been conducted to date have enabled
us to answer a number of questions related to epidemiology
and public health of cardiovascular and neurodegenerative
diseases, and to suggest hypotheses on possible links
between these two affections.
The research we are developing is structured around three
closely dependent topics :
1. Public health and epidemiology of cardiovascular diseases.
The evolution of the coronary disease and its determinants
are studied. Focused around a morbidity registry,
descriptive and analytical studies are developed on
vascular risk factors in general population, in particular
metabolic, on secondary prevention and on 10 year
coronary risk.
Work performed by UMR Inserm 744 concentrate on 3 key
topics :
1. Public health and epidemiology of cardiovascular
diseases
2. Search for the molecular determinants of cardiovascular
diseases via proteomic analysis and candidate gene
approaches
2. Identification of the molecular determinants od
cardiovascular diseases. We identify by comparative
proteomics new determinants of vascular remodeling
(abdominal aorta aneurisms) and venticular remodeling
(heart failure) in clinical studies.
3. Search for the molecular determinants of neurodegenerative diseases via transcriptomic analysis and
candidate gene approaches
3. Identification of molecular determinants of neurodegenerative diseases. Initiated by our work on the
relationships between vascular and neurodegenerative
risk, we identify determinants of the impairment of
cognitive functions, in particular Alzheimer’s disease, by
genomic and transcriptomic approaches in case-control
and prospective studies.
The permanent interaction of these issues through the
analysis of concepts and technical and strategic complementarities is critical to the innovative character of the
scientific production of our unit.
In the twenty past years, we have produced or been involved
in nearly 50 clinical and epidemiologic research studies.
Considering the competences of researchers of the unit in
the fields of biology and genetics, most of these studies gave
rise to the creation of biological banks including samples
from more than 45,000 individuals, to tackle the study of the
biological and genetic determinants of these conditions. The
volume of these banks has led us to set up a biological
resource centre to maintain these samples following good
practice recommendations.
The analysis of the trends of coronary diseases allows us to
estimate their impact in public health. The identification of
proteinic markers of remodeling supports the development
of more targeted approaches of prevention. The candidate
genes identified in the decline of cognitive functions direct
towards original physiopathological pathways, orienting to
new treatment hypotheses. The knowledge generated by
this molecular epidemiology enables us to apprehend the
complexity of the determinism of multifactorial diseases.
II - Organisational chart of the Unit (as at 1
November 2008)
2 - Prior activity
I - Previous scientific project objectives
attained (in the past 4 years)
There have been changes in the unit staff - Doctor Mahmoud
Zureik left the unit in January 2007 to turn to respiratory
diseases epidemiology in Inserm unit 700 in Paris. He
therefore no longer is in charge of team 1, which now is
supervised by Philippe Amouyel. In such a context, the
project focused on the characterisation of sub-clinical
vascular alterations using new imaging techniques was
limited to studies that are underway.
The results described in the present paragraph reports the
achievement of the past 4 years. The main objective of this
unit is to :
- Gain knowledge on the impact of environmental and
genetic susceptibility factors in the development,
prevention and therapeutic treatment of diseases
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Contents
B - Perspectives and
development 2010
Our project will be developed in the continuity of our
objectives of grain of knowledge on the impact of the
environmental and genetic determinants in the occurrence,
the evolution and the prevention and treatment of two major
ageing affections : cardiovascular and neurodegeneratives
diseases. Our project is organiszed according to three closely
interrelated axes :
1. Public health and epidemiology of cardiovascular diseases.
Our epidemiologic studies carried out on the cornary and
metabolic risk will be exploited in detail. The increase of life
expectancy and of cerebrovascular risk lead us to develop
a morbidity registry on stroke and a large European casecontrol study (4000 subjects) on cerebral artery dissection,
for which a whole genome analysis is scheduled.
2. Identification of molecular determinants of cardiovascular
diseases. The impact of the determinants of vascular and
ventricular remodeling we identified will be analyzed. We
will continue to implement our differential proteomic
techniques and will use these approaches in collaboration
on animal remodeling models. We will also apply our
approaches to the identification of markers of silent
cerebral ischaemia related to cardiac catheterization.
3. Identification of molecular determinants of neurodegenerative diseases. We will continue the genome analysis in
a large case-control study on Alzheimer’s disease (10 000
subjects) coupled to a European application study (10 000
other subjects). We will develop also functional analyses of
the markers we will identify.
These developments of adapted epidemiologic tools and
powerful molecular approaches will enable us to accelerate in
a competitive way the discovery of new determinants of the
diseases related to ageing and to open the way to new
preventive and therapeutic approaches.
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Contents
registers, which have been working in close cooperation for
more than twenty years, provide French data related to the trend
for cardiovascular diseases in the population. We also develop
cross-sectional epidemiological studies (population-based
investigation on a representative sample, clinical series) at
regular intervals and analytical studies (case-control &
prospective studies) to try to explain the trends observed in the
registry. These studies conducted by our teams have enabled us
to demonstrate or take part in the identification and assessment
of the impact of determinants for cardiovascular diseases.
Public Health
and Epidemiology
of Vascular Diseases
Philippe AMOUYEL
PU PH Lille 2
Group Members :
Dallongeville Jean, DR IPL
Dauchet Luc, AHU Lille 2
Dumont Julie, MCU Lille 2
Meirhaeghe-Hurez Aline, CR1 Inserm
Montaye Michèle, Médecin IPL
Goumidi Louisa, Research assistant Contrat UE
Beauchant Stéphanette, Médecin IPL
Cloez Anne, Infirmière IPL
Cottel Dominique, Médecin IPL
Cousin Béatrice, Infirmière IPL
Devoghelaere Christine, Médecin IPL
Dumont Marie-Pierre, Infirmière IPL
Graux Catherine, Médecin IPL
Lemaire Brigitte, Médecin IPL
Pygeire Marie, PhD Student Lille 2
Bodenant Marie, Master 2 Paris XI
Wyndels Karine, Master 2 Paris XI
Lecompte Sophie, Master 2 Student Lille 2
During our initial four-year project, we had set to ourselves as
objectives the completion of a number of epidemiological
studies, in particular :
1. a national, representative population-based investigation
on risk factors for the cardiovascular disease (Monalisa
investigation: National Arterial Risk Monitoring) following
the first two population-based investigations of the Monica
project (1985-87, 1995-97)
2. the validation of events 10 years later for the PRIME
prospective study on myocardial infarction
3. a European study on primary prevention of the coronary
disease (Euroaspire III investigation: EUROpean Action on
Secondary Prevention and Intervention to Reduce Events)
following the two previous ones (1995, 2000)
4. a longitudinal study on the acute coronary syndrome in
connection with the morbidity register
5. a case-control study on morbid obesity in adults
6. a case-control study on the risk of dissecting aneurysm of
the carotid
7. the development of a morbidity register for cerebrovascular diseases.
Key words :
Public heath. Molecular epidemiology. Aging. Cardiovascular
diseases (coronary heart disease, aneurysm, heart failure). Stroke.
Morbidity register. Risk factors. High throughout genomics.
Cardiovascular risk. Translational research. Prevention
Recruitments for the first three studies are over and findings
are now being worked upon. Recruitments are still underway
for the four last studies and data should be examined at the
end of 2009.
The objectives of this topic are :
- to gain more knowledge on the development of the
cardiovascular disease,
- to characterise its environmental and genetic determinants,
- to characterise sub-clinical vascular alterations using new
imaging techniques to estimate the cardiovascular risk.
Among the main preliminary findings obtained, the data of the
three French registers have shown that the average annual rates
of events for people aged 35 to 64 in France are 277/100,000 for
men and 54/100,000 for women (1997-2002) (Ruidavets et al,
2007; Montaye et al, 2007). Incidence rates are 240/100,000 for
men against 49/100,000 for women, and mortality rates reach
112/100,000 for men and 28/100,000 for women (Arveiler et al,
2007). In men, the standardised rates of coronary events have
tended to drop in Lille (-2.8% per annum) when they remained
stable in Strasbourg and have tended to increase in a nonsignificant way in Toulouse (+1.6% per annum). In women, the
analysis of trends does not show any significant change in rates,
whether centres may be considered separately or combined. For
both sexes, whatever the year, event rates are still higher in Lille
and Strasbourg than in Toulouse. The Euroaspire III study,
conducted in European coronary patients more than 6 months
after their events, has evidenced the increased prevalence of
obesity and overweight in the past 10 years. Finally, the initial
analyses of the Monalisa study have shown that in the global
population, the overweight level between 35 and 74 was higher
that regular estimates reported in France and that it affected two
thirds of men and 50% of women.
Descriptive, analytical and intervention epidemiology is required
to develop knowledge on the cardiovascular disease and
characterise its determinants. Part of our research efforts are
developed in the framework of the morbidity register of
ischemic cardiopathies in the Urban Community of Lille, which
has been keeping track of all myocardial infarction cases in a
population of approximately 1 million men and women aged 35
to 74, in a continuous and exhaustive manner since 1985. This
register, which is qualified by the “ Comité National de Registres
”, was initially created as part of the international monitoring
programme for cardiovascular diseases steered by the World
Health Organisation, MONICA project (Multinational
mONItoring of trends and determinants of CArdiovascular
diseases). To date, this programme still is the broadest
epidemiological study ever to have been launched on
cardiovascular diseases, the objective of which was to study the
trend of the incidence of cardiovascular diseases and
determinants which may account for such trend over at least 10
years. Thirty-eight registers in twenty-one countries were
involved in this study, including three located in France: “Urban
Community of Lille”, Bas-Rhin and Haute-Garonne. These three
During the past 4 years, we have also examined the impact of
certain environmental determinants on cardiovascular risk. Part
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Contents
of this work was focused on vascular risks related to the
metabolic syndrome and nutrition. The metabolic syndrome is
a clinical entity characterised by a combination of
cardiometabolic risk factors related to obesity (particularly in its
abdominal form) and insulin resistance. In the PRIME study, we
have evidenced an excess of coronary risk in subjects who met
existing definitions of the syndrome (Bataille et al, 2006). In the
MONICA population-based investigation, we could show a link
between the family history of early coronary disease and
metabolic syndrome suggesting that the latter could account
for part of the aggregation of coronary risk factors in families
(Dallongeville et al, 2006). This work is complemented by clinical
studies where we were able to assess the impact of the weight
loss induced by a hypo-caloric diet on the metabolic markers
of insulin resistance and on the appetite control hormones. We
demonstrated differentiated responses to test meals according
to lipid or carbohydrates content (Dallongeville et al, 2007;
Romon et al, 2006).
last study, we were able to demonstrate a link between the
increased carotid distensibility and risk of coronary disease in
the elderly (Leone et al, 2008), as well as the reduction in the
number of carotid plaques in women who regularly drink tea
(Debette et al, 2008). Several associations were also identified
between these sub-clinical vascular alterations and certain
genetic polymorphisms. For instance, a polymorphism of the
apolipoprotein E gene was associated with carotid plaques
(Debette et al, 2006) and several polymorphisms in the genes
of urea metabolism to the intima-media thickness variability
(Dumont et al, 2007a & 2007b).
The development and international scientific recognition of
these projects require the combination of a number of
conditions enabling the validation of results : sample size,
quality of recruitment, replication of results in various
populations, physiopathological hypotheses. This is why many
projects are conducted as part of international collaborative
efforts combining several teams to bring together several
hundreds or even thousands of subjects. The studies of the
register of coronary heart diseases are published in cooperation
with the other French centres at least, often with the Irish centre
of Belfast whose cardiovascular risk level is significantly higher
than the risk for France. The Euroaspire study results from
collaborative efforts with more than 20 European countries,
including 9 which were involved in the early stage of the study
in 1994, for trend analyses. Finally, our studies are also part of
larger consortiums to ensure sufficient power to answer certain
questions on vascular risk factors (The Fibrinogen Study
Collaboration, 2005) as well as in the Morgam project
(International pooling projectMOnica Risk, Genetics, Archiving
and Monograph) developed following the Monica programme.
Publications
We also explored the influence of genetic polymorphisms on
the risk of obesity, type-2 diabetes, or metabolic syndrome in
the MONICA population-based survey or in case-control studies
on obesity or type-2 diabetes. We could demonstrate that
APOA4 (Dallongeville et al, 2005), KLF2 (Meirhaeghe et al,
2006a) and perilipin genes (Meirhaeghe et al, 2006b) do not
seem to be involved in the regulation of body weight. In
contrast, we could show that a polymorphism of the CART gene
increases the risk of obesity (Guerardel et al, 2005) and
atherosclerosis risk (Vasseur et al, 2007). We have also found that
the polymorphisms of BNP (Meirhaeghe et al, 2007),
adiponectine (Vasseur et al, 2005), HNF-4 (Vaxillaire et al,
2005), KFL11 (Neve et al, 2005), KFL10 and SMAD7 genes
(Gutierrez-Aguilar et al, 2007) modulated the risk of type-2
diabetes and that a polymorphism of the LXR gene (liver X
receptor) is linked to higher circulating HDL-cholesterol rates
and a reduced risk of metabolic syndrome (Legry et al, 2008).
Finally, we have shown that a haplotype of the PPARG gene is
associated with a 2.3-fold increase in the metabolic syndrome
risk (Meirhaeghe et al, 2005) and that the Pro12Ala
polymorphism of the PPARG gene was a risk factor for
prematurity (risk multiplied by 2) in 2 independent cohorts of
Irish teenagers and young adults (Meirhaeghe et al, 2007).
2007
Appleton KM, Woodside JV, Yarnell JW, Arveiler D, Haas B,
Amouyel P, Montaye M, Ferrières J, Ruidavets JB, Ducimetière P,
Bingham A, Evans A ; for the PRIME Study Group.
Type A behaviour and consumption of an atherogenic diet : No
association in the PRIME study.
Appetite, 2007, 49:554-560.
Appleton KM, Woodside JV, Yarnell JW, Arveiler D, Haas B,
Amouyel P, Montaye M, Ferrières J, Ruidavets JB, Ducimetière P,
Bingham A, Evans A ; for the PRIME Study Group.
Depressed mood and dietary fish intake : Direct relationship or indirect
relationship as a result of diet and lifestyle ?
J Affect Disord, 2007, 104:217-223.
Boddaert J, Kinugawa K, Lambert JC, Boukhtouche F, Zoll J,
Merval R, Blanc-Brude O, Mann D, Berr C, Vilard J, Garabedian B,
Silvestre JS, Duyckaerts C, Amouyel P, Mariani J, Tedgui A, Mallat Z.
Evidence of a role for lactadherin in Alzheimer's disease.
Am J Pathol, 2007, 170:921-929.
Dallongeville J, Gruson E, Dallinga-Thie G, Pigeyre M, Gomila S, Romon M.
Effect of weight loss on the postprandial response to high-fat and highcarbohydrate meals in obese women.
Eur J Clin Nutr, 2007, 61:711-718.
The third aspect of this research program is the characterisation
of sub-clinical vascular alterations using non-invasive imaging
techniques to estimate the cardiovascular risk. These research
efforts were developed on the basis of measurements made via
carotid echography in two epidemiologic studies: the EVA study
(Assessment of Artery Ageing) and “Etude des Trois Cités”. In this
de Groote P, Mouquet F, Dallongeville J, Lamblin N, Bauters C.
The impact of the AMPD1 gene polymorphism on exercise capacity, other
prognostic parameters, and survival in patients with stable congestive
heart failure. A study on 686 consecutive patients.
Am Heart J, 2007, 153:e15.
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Contents
De Henauw S, Gottrand F, De Bourdeaudhuij I, Gonzalez-Gross M,
Leclercq C, Kafatos A, Molnar D, Marcos A, Castillo M, Dallongeville J,
Gilbert CC, Bergman P, Widhalm K, Manios Y, Breidenassel C,
Kersting M, Moreno LA, on behalf of the HELENA Study Group.
Nutritional status and lifestyles of adolescents from a public health
prespective. The HELENA Project - Healthy Lifestyle in Europe by Nutrition
in Adolescence.
J Publ Health, 2007, 15:187-197.
Graham I, Atar D, Borch-Johnsen K, Boysen G, Burell G, Cifkova R,
Dallongeville J, et al.
European guidelines on cardiovascular disease prevention in clinical
practice: executive summary : Fourth Joint Task Force of the European
Society of Cardiology and Other Societies on Cardiovascular Disease
Prevention in Clinical Practice : Executive summary.
Eur Heart J, 2007, 28:2375-2414.
Dallongeville J, De Backer G, Ebrahim S, Gjelsvik B, HerrmannLingen C, Hoes A, Humphries S, Knapton M, Perk J, Priori SG,
Pyorala K, Reiner Z, Ruilope L, Sans-Menendez S, Op Reimer WS,
Weissberg P, Wood D, Yarnell J, Zamorano JL.
ESC Committee for Practice Guidelines. European guidelines on
cardiovascular disease prevention in clinical practice : Executive summary.
Atherosclerosis, 2007, 194:1-45.
Dumont J, Zureik M, Cottel D, Montaye M, Ducimetière P,
Amouyel P, Brousseau T.
Association of arginase 1 gene polymorphisms with the risk of myocardial
infarction and common carotid intima-media thickness.
J Med Genet, 2007, 44:526-531.
Dumont J, Zureik M, Bauters C, Grupposo MC, Cottel D,
Montaye M, Hamon M, Ducimetière P, Amouyel P, Brousseau T.
Association of OAZ1 Gene Polymorphisms With Subclinical and Clinical
Vascular Events.
Arterioscler Thromb Vasc Biol, 2007, 27:2120-2126
Guyant-Maréchal L, Rovelet-Lecrux A, Goumidi L, Cousin E,
Hannequin D, Raux G, Penet C, Ricard S, Macé S, Amouyel P,
Deleuze JF, Frebourg T, Brice A, Lambert JC, Campion D.
Variations in the APP promoter region and risk to Alzheimer’s disease.
Neurology, 2007, 68:632-633.
Emerging Risk Factors Collaboration, Danesh J, Erqou S, Walker M,
Thompson SG, Tipping R, Ford C, Pressel S, Walldius G, Jungner I,
Folsom AR, Chambless LE, Knuiman M, Whincup PH, Wannamethee SG,
Morris RW, Willeit J, Kiechl S, Santer P, Mayr A, Wald N, Ebrahim S,
Lawlor DA, Yarnell JW, Gallacher J, Casiglia E, Tikhonoff V, Nietert PJ,
Sutherland SE, Bachman DL, Keil JE, Cushman M, Psaty BM, Tracy RP,
Tybjaerg-Hansen A, Nordestgaard BG, Frikke-Schmidt R, Giampaoli S,
Palmieri L, Panico S, Vanuzzo D, Pilotto L, Simons L, McCallum J,
Friedlander Y, Fowkes FG, Lee AJ, Smith FB, Taylor J, Guralnik J,
Phillips C, Wallace R, Blazer D, Khaw KT, Jansson JH, Donfrancesco C,
Salomaa V, Harald K, Jousilahti P, Vartiainen E, Woodward M,
D'Agostino RB, Wolf PA, Vasan RS, Pencina MJ, Bladbjerg EM,
Jorgensen T, Moller L, Jespersen J, Dankner R, Chetrit A, Lubin F,
Rosengren A, Wilhelmsen L, Lappas G, Eriksson H, Bjorkelund C,
Cremer P, Nagel D, Tilvis R, Strandberg T, Rodriguez B, Bouter LM,
Heine RJ, Dekker JM, Nijpels G, Stehouwer CD, Rimm E, Pai J, Sato S,
Iso H, Kitamura A, Noda H, Goldbourt U, Salomaa V, Salonen JT,
Nyyssönen K, Tuomainen TP, Deeg D, Poppelaars JL, Meade T, Cooper
J, Hedblad B, Berglund G, Engstrom G, Döring A, Koenig W, Meisinger C,
Mraz W, Kuller L, Selmer R, Tverdal A, Nystad W, Gillum R, Mussolino M,
Hankinson S, Manson J, De Stavola B, Knottenbelt C, Cooper JA, Bauer
KA, Rosenberg RD, Sato S, Naito Y, Holme I, Nakagawa H, Miura H,
Ducimetière P, Jouven X, Crespo C, Garcia-Palmieri M, Amouyel P et al.
The Emerging Risk Factors Collaboration : analysis of individual data on
lipid, inflammatory and other markers in over 1.1 million participants in
104 prospective studies of cardiovascular diseases.
Eur J Epidemiol, 2007, 22:839-869.
Helbecque N, Cottel D, Hermant X, Amouyel P.
Impact of the matrix metalloproteinase MMP-3 on dementia.
Neurobiol Aging, 2007, 28:1215-1220.
Komajda M, Amouyel P, Johnson N, Bergougnoux L, Laperche T,
de Groote P, Jaillon P, Cohen-Solal A.
Comité scientifique d'étude de KEOPS et des investigateurs. Treating heart
failure with carvedilol in private practice (initiating treatment and followup at one year). The KEOPS study.
Arch Mal Coeur Vaiss, 2007, 100:818-826.
Lambert JC, Ferreira S, Gussekloo J, Christiansen L, Brysbaert B,
Slagboom PE, Cottel D, Petit T, Hauw JJ, Dekosky ST, Richard F,
Berr C, Lendon CL, Kamboh IM, Mann D, Christensen K,
Westendorp R, Amouyel P.
Evidence for the association of the S100beta gene with low cognitive
performance and dementia in the elderly.
Mol Psychiatry, 2007, 12:870-880.
Lambert JC, Amouyel P.
Genetic heterogeneity of Alzheimer's disease: Complexity and advances.
Psychoneuroendocrinology, 2007, 32 Suppl 1:S62-S70.
Meirhaeghe A, Sandhu MS, McCarthy MI, de Groote P, Cottel D,
Arveiler D, Ferrières J, Groves CJ, Hattersley AT, Hitman GA, Walker
M, Wareham NJ, Amouyel P.
Association between the T-381C polymorphism of the brain natriuretic
peptide gene and risk of type 2 diabetes in human populations.
Hum Mol Genet, 2007, 16:1343-1350.
Evans A, Marques-Vidal P, Ducimetière P, Montaye M, Arveiler D,
Bingham A, Ruidavets JB, Amouyel P, Haas B, Yarnell J, Ferrières J,
Fumeron F, Luc G, Kee F, Cambien F.
Patterns of alcohol consumption and cardiovascular risk in northern
ireland and france.
Ann Epidemiol, 2007, 17(5 Suppl):S75-80.
Meirhaeghe A, Boreham CA, Murray LJ, Richard F, Davey Smith G,
Young IS, Amouyel P.
A possible role for the PPARG Pro12Ala polymorphism in preterm birth.
Diabetes, 2007, 56:494-498.
practice: full text. Fourth Joint Task Force of the European Society of
Cardiology and other societies on cardiovascular disease prevention in
clinical practice : Full text.
Eur J Cardiovasc Prev Rehabil, 2007, 14 Suppl 2:S1-S113.
Montalescot G, Dallongeville J, Van Belle E, Rouanet S, Baulac C,
Degrandsart A, Vicaut E ; for the OPERA Investigators .
STEMI and NSTEMI : are they so different ? 1 year outcomes in acute myocardial infarction as defined by the ESC/ACC definition (the OPERA registry).
Eur Heart J, 2007, 28:1409-1417.
practice: executive summary. Fourth Joint Task Force of the European
Society of Cardiology and other societies on cardiovascular disease
prevention in clinical practice : Executive summary.
Eur J Cardiovasc Prev Rehabil, 2007, 14 Suppl 2:E1-E40.
Puig JG, Marre M, Kokot F, Fernandez M, Jermendy G, Opie L,
Moyseev V, Scheen A, Ionescu-Tirgoviste C, Saldanha MH,
Halabe A, Williams B, Mion D, Ruiz M, Hermansen K, Tuomilehto J,
Finizola B, Gallois Y, Amouyel P, Ollivier JP, Asmar R.
Efficacy of indapamide SR compared with enalapril in elderly
hypertensive patients with type 2 diabetes.
Am J Hypertens, 2007, 20:90-97.
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Ruidavets JB, Bongard V, Dallongeville J, Arveiler D, Ducimetière P,
Perret B, Simon C, Amouyel P, Ferrières J.
High consumptions of grain, fish, dairy products and combinations of
these are associated with a low prevalence of metabolic syndrome.
J Epidemiol Community Health, 2007, 61:810-817.
Campagne F, Lambert JC, Dreses-Werringloer U, Vingtdeux V,
Lendon C, Campion D, Amouyel P, Lee AT, Gregersen PK, Davies P,
Marambaud P.
CALHM1 association with Alzheimer's disease risk response.
Cell, 2008, 135:994-996.
Troughton JA, Woodside JV, Young IS, Arveiler D, Amouyel P,
Ferrières J, Ducimetière P, Patterson CC, Kee F, Yarnell JW, Evans A.
Homocysteine and coronary heart disease risk in the PRIME study.
Chaix B, Ducimetière P, Lang T, Haas B, Montaye M, Ruidavets JB,
Arveiler D, Amouyel P, Ferrières J, Bingham A, Chauvin P.
Residential environment and blood pressure in the PRIME Study : is the
association mediated by body mass index and waist circumference ?
J Hypertens, 2008, 26:1078-1084.
Troughton JA, Woodside JV, Young IS, Arveiler D, Amouyel P,
Ferrières J, Ducimetière P, Patterson CC, Kee F, Yarnell JW, Evans A.
PRIME Study Group. Bilirubin and coronary heart disease risk in the
Prospective Epidemiological Study of Myocardial Infarction (PRIME).
Eur J Cardiovasc Prev Rehabil, 2007, 14:79-84.
Chapuis J, Hannequin D, Pasquier F, Bentham P, Brice A, Leber I,
Frebourg T, Deleuze JF, Cousin E, Thaker U, Amouyel P, Mann D,
Lendon C, Campion D, Lambert JC.
Association study of the GAB2 gene with the risk of developing
Alzheimer's disease.
Neurobiol Dis, 2008, 30:103-106.
Vasseur F, Guerardel A, Barat-Houari M, Cottel D, Amouyel P,
Froguel P, Helbecque N.
Impact of a CART promoter genetic variation on plasma lipid profile in a
general population.
Mol Genet Metab, 2007, 90:199-204.
Chapuis J, Moisan F, Mellick G, Elbaz A, Pasquier F, Hannequin D,
Lendon C, Campion D, Amouyel P, Lambert JC.
Association study of the NEDD9 gene with the risk of developing
Alzheimer's and Parkinson's disease.
Hum Mol Genet, 2008, 17:2863-2867.
Vicente-Rodriguez G, Libersa C, Mesana MI, Béghin L, Iliescu C,
Moreno Aznar LA, Dallongeville J, Gottrand F.
Healthy Lifestyle by Nutrition in Adolescence (HELENA). A New EU Funded
Project.
Therapie 2007; 62:259-270.
Chouraki V, Wagner A, Ferrières J, Kee F, Bingham A, Haas B,
Ruidavets J-B, Evans A, Ducimetière P, Amouyel P, Dallongeville J.
Waist circumference, smoking and 10 years coronary artery disease risk
in middle aged men : the PRIME study.
Amouyel P.
Epidémiologie des syndromes coronaires aigus.
In : Cardiologie et maladies cardiovasculaires.
Ed. Société Française de Cardiologie. Masson, 2007, 88-94.
Cieniewski-Bernard C, Mulder P, Henry JP, Drobecq H, Dubois E,
Pottiez G, Thuillez C, Amouyel P, Richard V, Pinet F.
Proteomic analysis of left ventricular remodelling in an experimental
model of heart failure.
J Proteome Res, 2008, 7:5004-5016.
Bongard V, Dallongeville J.
Diabète et Syndrome Métabolique.
In : Cardiologie et maladies cardiovasculaires. Ed. Société Française de
Cardiologie. Masson, 2007, 109-112.
Cieniewski-Bernard C, Acosta A, Dubois E, Lamblin N, Beseme O,
Chwastyniak M, Amouyel P, Bauters C, Pinet F.
Proteomic analysis in cardiovascular diseases.
Clin Exp Pharmacol Physiol, 2008, 35:362-366.
Dallongeville J.
Evaluation du risque cardiovasculaire.
In : Cardiologie et maladies cardiovasculaires. Ed. Société Française de
Cardiologie. Masson, 2007, 265-268.
Dallongeville J, Cottel D, Wagner A, Ducimetière P, Ruidavets JB,
Arveiler D, Bingham A, Ferrières J, Amouyel P, Meirhaeghe A.
The APOA5 Trp19 allele is associated with metabolic syndrome via its
association with plasma triglycerides.
BMC Med Genet, 2008, 9:84.
Dallongeville J, Dauchet L, Amouyel P.
Epidémiologie de l’Obésité Abdominale.
In : L’obésité abdominale, une maladie métabolique. Ed. Després JP.
Collection Pathologie, Science, Formation. Libbey J, EUROTEXT 2007, 5-28.
Dallongeville J, Bringer J, Bruckert E, Charbonnel B, Dievart F,
Komajda M, Pouchain D, Amouyel P.
Abdominal obesity is associated with ineffective control of cardiovascular
risk factors in primary care in France.
Diabetes Metab, 2008, 34:606-611.
2008
Biggio V, Renneville A, Nibourel O, Philippe N, Terriou L, Roumier C,
Amouyel P, Cottel D, Castaigne S, Dombret H, Thomas X, Fenaux P,
Preudhomme C.
Recurrent in-frame insertion in C/EBPalpha TAD2 region is a polymorphism without prognostic value in AML.
Leukemia, 2008, 22:655-657.
Dauchet L, Dallongeville J.
Fruit and vegetables and cardiovascular disease : epidemiological
evidence from the non-Western world.
Br J Nutr, 2008, 99:219-220.
Bruandet A, Richard F, Bombois S, Maurage CA, Masse I,
Amouyel P, Pasquier F.
Cognitive decline and survival in Alzheimer’s disease according to
education level.
Dement Geriatr Cogn Disord, 2008, 25:74-80.
Debette S, Courbon D, Leone N, Gariépy J, Tzourio C, Dartigues JF,
Barberger-Gateau P, Ritchie K, Alpérovitch A, Amouyel P,
Ducimetière P, Zureik M.
Tea consumption is inversely associated with carotid plaques in women.
Arterioscler Thromb Vasc Biol, 2008, 28:353-359.
Bruandet A, Richard F, Tzourio C, Berr C, Dartigues JF,
Alpérovitch A, Amouyel P, Helbecque N.
Haplotypes across ACE and the risk of Alzheimer's disease : The Three-City
Study.
J Alzheimers Dis, 2008, 13:333-339.
Debette S, Leone N, Courbon D, Gariépy J, Tzourio C, Dartigues JF,
Ritchie K, Ducimetière P, Amouyel P, Zureik M.
Calf circumference is inversely associated with carotid plaques.
Stroke, 2008, 39:2958-2965.
114
Contents
Dreses-Werringloer U, Lambert JC, Vingtdeux V, Zhao H, Vais H,
Siebert A, Jain A, Koppel J, Rovelet-Lecrux A, Hannequin D,
Pasquier F, Galimberti D, Scarpini E, Mann D, Lendon C, Campion D,
Amouyel P, Davies P, Foskett JK, Campagne F, Marambaud P.
A polymorphism in CALHM1 influences Ca2+ homeostasis, Abeta levels,
and Alzheimer's disease risk.
Cell, 2008, 133:1149-1161.
Troughton JA, Woodside JV, Yarnell JW, Arveiler D, Amouyel P,
Ferrières J, Ducimetière P, Patterson CC, Luc G ; on behalf of the
PRIME Study Group.
Paraoxonase activity and coronary heart disease risk in healthy middleaged males : The PRIME study.
Combris P, Amiot-Carlin M-J, Caillavet F, Causse M, Dallongeville J,
Padilla M, Renard C, Soler L-G.
Les fruits et légumes dans l'alimentation. Enjeux et déterminants de la
consommation. Série Expertise collective.
Éditeur Quae, Versailles, France. 2008.
Dupont A, Chwastyniak M, Beseme O, Guihot AL, Drobecq H,
Amouyel P, Pinet F.
Application of saturation dye 2D-DIGE proteomics to characterize
proteins modulated by oxidized low density lipoprotein treatment of
human macrophages.
J Proteome Res, 2008, 7:3572-3582.
2009
Acosta-Martin AE, Chwastyniak M, Beseme O, Drobecq H,
Amouyel P, Pinet F.
Impact of incomplete DNase I treatment on human macrophage
analysis.
Proteomics Clin Appl, 2009, 3:1-11.
Empana JP, Canoui-Poitrine F, Luc G, Juhan-Vague I, Morange PE,
Arveiler D, Ferrières J, Amouyel P, Bingham A, Montaye M, Ruidavets JB,
Haas B, Evans A, Ducimetière P, on behalf of The PRIME Study Group :
Contribution of novel biomarkers to incident stable angina and acute
coronary syndrome. The PRIME Study.
Eur Heart J, 2008, 29:1966-1974.
Helbecque N, Codron V, Cottel D, Amouyel P.
An apolipoprotein A-I gene promoter polymorphism associated with
cognitive decline, but not with Alzheimer's disease.
Ahluwalia N, Ferrières J, Dallongeville J, Simon C, Ducimetière P,
Amouyel P, Arveiler D, Ruidavets JB.
Association of macronutrient intake patterns with being overweight in a
population-based random sample of men in France.
Diabetes Metab, 2009, 35:129-136.
Legry V, Cottel D, Ferrières J, Deroide T, Amouyel P, Meirhaeghe A.
Association between liver X receptor alpha gene polymorphisms and
metabolic syndrome in French populations.
Int J Obes, (Lond) 2008, 32:421-428.
Allouch M, Zhong YZ, Riddell JW, Sabatier R, Hamon M.
Transradial coronary rotational atherectomy using 5-French guiding
catheters.
Chin Med J (Engl), 2009, 122:1356-1358.
Leone N, Ducimetière P, Gariépy J, Courbon D, Tzourio C, Dartigues JF,
Ritchie K, Alpérovitch A, Amouyel P, Safar ME, Zureik M.
Distension of the carotid artery and risk of coronary events.
The Three-City Study.
Amouyel P, Mismetti P, Langkilde LK, Jasso-Mosqueda G,
Nelander K, Lamarque H.
INR variability in atrial fibrillation : a risk model for cerebrovascular events.
Eur J Intern Med, 2009, 20:63-69.
Asplund K, Karvanen J, Giampaoli S, Jousilahti P, Niemelä M,
Broda G, Cesana G, Dallongeville J, Ducimetriere P, Evans A,
Ferrières J, Haas B, Jorgensen T, Tamosiunas A, Vanuzzo D,
Wiklund PG, Yarnell J, Kuulasmaa K, Kulathinal S; MORGAM Project.
Relative risks for stroke by age, sex, and population based on follow-up
of 18 European populations in the MORGAM Project.
Stroke, 2009, 40:2319-2326.
Lieb W, Zeller T, Mangino M, Götz A, Braund P, Wenzel JJ, Horn C,
Proust C, Linsel-Nitschke P, Amouyel P, Bruse P, Arveiler D, König IR,
Ferrières J, Ziegler A, Balmforth AJ, Evans A, Ducimetière P,
Cambien F, Hengstenberg C, Stark K, Hall AS, Schunkert H,
Blankenberg S, Samani NJ, Erdmann J, Tiret L.
Lack of association of genetic variants in the LRP8 gene with familial and
sporadic myocardial infarction.
J Mol Med, 2008, 86:1163-1170.
Barthélémy O, Beygui F, Vicaut E, Rouanet S, Van Belle E, Baulac C,
Degrandsart A, Dallongeville J, Montalescot G ; OPERA Investigators.
Relation of high concentrations of plasma carboxy-terminal telopeptide
of collagen type I with outcome in acute myocardial infarction.
Am J Cardiol, 2009, 104:904-909.
Moreno LA, Gonzalez-Gross M, Kersting M, Molnar D, de Henauw S,
Beghin L, Sjöström M, Hagströmer M, Manios Y, Gilbert CC,
Ortega FB, Dallongeville J, Arcella D, Wärnberg J, Hallberg M,
Fredriksson H, Maes L, Widhalm K, Kafatos AG and Marcos A,
on behalf of the HELENA Study Group.
Assessing, understanding and modifying nutritional status, eating habits
and physical activity in European adolescents : The HELENA (Healthy
Lifestyle in Europe by Nutrition in Adolescence) Study.
Public Health Nutr, 2008, 11:288-299.
Bensemain F, Hot D, Ferreira S, Dumont J, Bombois J, Maurage CA,
Huot L, Hermant X, Levillain E, Hubans C, Hansmannel F, Chapuis J,
Lemoine Y, Hauw JJ, Schraen S, Lemoine Y, Buée L, Berr C, Mann D,
Pasquier F, Amouyel P, Lambert JC.
Evidence for induction of the ornithine transcarbamylase expression in
Mol Psychiatry, 2009, 14:106-116.
Pinet F, Beseme O, Cieniewski-Bernard C, Drobecq H, Jourdain S,
Lamblin N, Amouyel P, Bauters C.
Predicting left ventricular remodeling after a first myocardial infarction
by plasma proteome analysis.
Proteomics, 2008, 8:1798-1808.
Beygui F, Montalescot G, Vicaut E, Rouanet S, Van Belle E, Baulac C,
Degrandsart A, Dallongeville J ; OPERA Investigators.
Aldosterone and long-term outcome after myocardial infarction :
A substudy of the french nationwide Observatoire sur la Prise en charge
hospitalière, l'Evolution à un an et les carRactéristiques de patients
présentant un infArctus du myocarde avec ou sans onde Q (OPERA) study.
Am Heart J, 2009, 157:680-687.
Sabouret P, Cacoub P, Dallongeville J, Krempf M, Mas JL, Pinel JF,
Priollet P, Steg G, Taminau D, Montalescot G ; for the REACH Registry
investigators.
REACH : International prospective observational registry in patients at
risk of atherothrombotic events. Results for the French arm at baseline
and one year.
Arch Cardiovasc Dis, 2008, 101:81-88.
Bokor S, Amouyel P, Dallongeville J.
Which measure of adiposity for primary care ?
Int J Clin Pract, 2009, 63:1270-1272.
115
Contents
Bruandet A, Richard F, Bombois S, Maurage CA, Deramecourt V,
Lebert F, Amouyel P, Pasquier F.
Alzheimer's disease with cerebrovascular disease and vascular dementia
: clinical features and course compared with Alzheimer's disease.
J Neurol Neurosurg Psychiatry, 2009, 80:133-139.
Debette S, Metso TM, Pezzini A, Engelter ST, Leys D, Lyrer P,
Metso AJ, Brandt T, Kloss M, Lichy C, Hausser I, Touzé E, Markus HS,
Abboud S, Caso V, Bersano A, Grau A, Altintas A, Amouyel P,
Tatlisumak T, Dallongeville J, Grond-Ginsbach C ; CADISP group.
CADISP-genetics : an International project searching for genetic risk
factors of cervical artery dissections.
Int J Stroke, 2009, 4:224-230.
Canoui-Poitrine F, Luc G, Juhan-Vague I, Morange PE, Arveiler D,
Ferrieres J, Amouyel P, Bingham A, Montaye M, Ruidavets JB,
Haas B, Evans A, Ducimetiere P, Empana JP; on behalf of The PRIME
Study Group.
Respective contribution of conventional risk factors and antihypertensive
treatment to stable angina pectoris and acute coronary syndrome as first
presentation of coronary heart disease. The PRIME Study.
Delhaye C, Sudre A, Lemesle G, Maréchaux S, Broucqsault D,
Hennache B, Bauters C, Lablanche JM.
Preprocedural high-sensitivity C-reactive protein predicts death or
myocardial infarction but not target vessel revascularization or stent
thrombosis after percutaneous coronary intervention.
Cardiovasc Revasc Med, 2009, 10:144-150.
Chapuis J, Boscher M, Bensemain F, Cottel D, Amouyel P, Lambert JC.
Association study of the paraoxonase 1 gene with the risk of developing
Neurobiol Aging, 2009, 30:152-156.
Deschaintre Y, Richard F, Leys D, Pasquier F.
Treatment of vascular risk factors is associated with slower decline in
Alzheimer’s disease.
Neurology, 2009, 73:674-680.
Chapuis J, Hot D, Hansmannel F, Kerdraon O, Ferreira S, Hubans C,
Maurage CA, Huot L, Bensemain F, Laumet G, Ayral AM, Fievet N,
Hauw JJ, DeKosky ST, Lemoine Y, Iwatsubo T, Wavrant-De Vrièze F,
Dartigues JF, Tzourio C, Buee L, Pasquier F, Berr C, Mann D,
Lendon C, Alpérovitch A, Kamboh MI, Amouyel P, Lambert JC.
Transcriptomic and genetic studies Identify IL-33 as a candidate gene for
Mol Psychiatry, 2009, 14:1004-1016.
Do HQ, Nazih H, Luc G, Arveiler D, Ferrières J, Evans A, Amouyel P,
Cambien F, Ducimetière P, Bard JM.
Influence of cholesteryl ester transfer protein, peroxisome proliferatoractivated receptor alpha, apolipoprotein E, and apolipoprotein A-I
polymorphisms on high-density lipoprotein cholesterol, apolipoprotein
A-I, lipoprotein A-I, and lipoprotein A-I:A-II concentrations : the
Prospective Epidemiological Study of Myocardial Infarction study.
Metabolism, 2009, 58:283-289.
Clément K, Stunff CL, Meirhaeghe A, Dechartres A, Ferrieres J,
Basdevant A, Boitard C, Amouyel P, Bougnères P.
In obese and non-obese adults, the cis-regulatory rs361072 promoter
variant of PIK3CB is associated with insulin resistance not with type 2
diabetes.
Mol Genet Metab. 2009; 96(3):129-132.
Dumont J, Meroufel D, Bauters C, Hansmannel F, Bensemain F,
Cottel D, Hamon M, Lambert JC, Ducimetière P, Amouyel P,
Zureik M, Brousseau T.
Association of ornithine transcarbamylase gene polymorphisms with
hypertension and coronary artery vasomotion.
Am J Hypertens, 2009, 22:993-1000.
Clergeau M-R, Hamon M, Morello R, Saloux E, Viader F, Hamon M.
Silent cerebral infarcts in patients with pulmonary embolism and a patent
foramen ovale : a prospective diffusion-weighted magnetic resonnance
imaging study.
Stroke, 2009, 40:3758-3762.
Emerging Risk Factors Collaboration, Erqou S, Kaptoge S, Perry PL,
Di Angelantonio E, Thompson A, White IR, Marcovina SM, Collins R,
Thompson SG, Danesh J.
Lipoprotein(a) concentration and the risk of coronary heart disease,
stroke, and nonvascular mortality.
JAMA, 2009, 302:412-423.
Coronary Artery Disease Consortium, Samani NJ, Deloukas P,
Erdmann J, Hengstenberg C, Kuulasmaa K, McGinnis R, Schunkert H,
Soranzo N, Thompson J, Tiret L, Ziegler A.
Large scale association analysis of novel genetic loci for coronary artery
disease.
Emerging Risk Factors Collaboration, Di Angelantonio E, Sarwar N,
Perry P, Kaptoge S, Ray KK, Thompson A, Wood AM, Lewington S,
Sattar N, Packard CJ, Collins R, Thompson SG, Danesh J.
Major lipids, apolipoproteins, and risk of vascular disease.
JAMA, 2009, 302:1993-2000.
Dallongeville J, Iribarren C, Ferrières J, Lyon L, Evans A, Go AS,
Arveiler D, F
ortmann SP, Ducimetière P, Hlatky MA, Amouyel P, Southwick A,
Quertermous T, Meirhaeghe A. Peroxisome proliferator-activated receptor
gamma polymorphisms and coronary heart disease.
PPAR Res, 2009, 2009:543746.
Empana JP, Dauvilliers Y, Dartigues JF, Ritchie K, Gariepy J,
Jouven X, Tzourio C, Amouyel P, Besset A, Ducimetiere P.
Excessive daytime sleepiness is an independent risk indicator for
cardiovascular mortality in community-dwelling elderly : the three city study.
Stroke, 2009, 40:1219-1224.
Ferrières J, Bongard V, Dallongeville J, Arveiler D, Cottel D, Haas B,
Wagner A, Amouyel P, Ruidavets JB.
Trends in plasma lipids, lipoproteins and dyslipidaemias in French adults,
1996-2007.
Dauchet L, Amouyel P, Dallongeville J ; Medscape.
Fruits, vegetables and coronary heart disease.
Nat Rev Cardiol, 2009, 6:599-608.
Debette S, Bevan S, Dartigues JF, Sitzer M, Lorenz M, Ducimetière P,
Amouyel P, Markus HS.
Fractalkine receptor/ligand genetic variants and carotid intima-media
thickness.
Stroke, 2009, 40:2212-2214.
Fibrinogen Studies Collaboration.
Measures to assess the prognostic ability of the stratified Cox proportional
hazards model.
Stat Med, 2009, 28:389-411.
116
Contents
Fibrinogen Studies Collaboration, Jackson D, White I, Kostis JB,
Wilson AC, Folsom AR, Wu K, Chambless L, Benderly M, Goldbourt
U, Willeit J, Kiechl S, Yarnell JW, Sweetnam PM, Elwood PC, Cushman
M, Psaty BM, Tracy RP, Tybjaerg-Hansen A, Haverkate F, de Maat MP,
Thompson SG, Fowkes FG, Lee AJ, Smith FB, Salomaa V, Harald K,
Rasi V, Vahtera E, Jousilahti P, D'Agostino R, Kannel WB, Wilson PW,
Tofler G, Levy D, Marchioli R, Valagussa F, Rosengren A, Wilhelmsen
L, Lappas G, Eriksson H, Cremer P, Nagel D, Curb JD, Rodriguez B,
Yano K, Salonen JT, Nyyssönen K, Tuomainen TP, Hedblad B,
Engström G, Berglund G, Loewel H, Koenig W, Hense HW,
Meade TW, Cooper JA, De Stavola B, Knottenbelt C, Miller GJ,
Cooper JA, Bauer KA, Rosenberg RD, Sato S, Kitamura A, Naito Y,
Iso H, Salomaa V, Harald K, Rasi V, Vahtera E, Jousilahti P, Palosuo T,
Ducimetiere P, Amouyel P, Arveiler D, Evans AE, Ferrieres J, JuhanVague I, Bingham A, Schulte H, Assmann G, Cantin B, Lamarche B,
Despres JP, Dagenais GR, Tunstall-Pedoe H, Lowe GD, Woodward M,
Ben-Shlomo Y, Davey Smith G, Palmieri V, Yeh JL, Meade TW,
Rudnicka A, Brennan P, Knottenbelt C, Cooper JA, Ridker P,
Rodeghiero F, Tosetto A, Shepherd J, Lowe GD, Ford I, Robertson M,
Brunner E, Shipley M, Feskens EJ, Di Angelantonio E, Kaptoge S,
Lewington S, Lowe GD, Sarwar N, Thompson SG, Walker M,
Watson S, White IR, Wood AM, Danesh J.
Systematically missing confounders in individual participant data metaanalysis of observational cohort studies.
Stat Med, 2009, 28:1218-1237.
Hachulla E, Carpentier P, Gressin V, Diot E, Allanore Y, Sibilia J,
Launay D, Mouthon L, Jego P, Cabane J, de Groote P, Chabrol A,
Lazareth I, Guillevin L, Clerson P, Humbert M; ItinérAIRSclérodermie Study Investigators.
Risk factors for death and the 3-year survival of patients with systemic
sclerosis : the French ItinérAIR-Sclérodermie study.
Rheumatology (Oxford), 2009, 48:304-308.
Fibrinogen Studies Collaboration.
Correcting for multivariate measurement error by regression calibration
in meta-analyses of epidemiological studies.
Stat Med, 2009, 28:1067-1092.
An age effect on the association of common variants of ACE with
Neurosci Lett, 2009, 461:181-184.
Gardette V, Bongard V, Dallongeville J, Arveiler D, Bingham A,
Ruidavets JB, Amouyel P, Haas B, Ducimetière P, Ferrières J.
Ten-year all-cause mortality in presumably healthy subjects on lipidlowering drugs (from the Prospective Epidemiological Study of
Myocardial Infarction [PRIME] prospective cohort).
Am J Cardiol, 2009, 103:381-386.
Helbecque N, Cottel D, Amouyel P.
Low-density lipoprotein receptor-related protein 8 gene polymorphisms
and dementia.
Hamon M, Rasmussen LH, Manoukian SV, Cequier A, Lincoff AM,
Rupprecht HJ, Gersh BJ, Mann T, Bertrand ME, Mehran R, Stone GW.
Choice of arterial access site and outcomes in patients with acute coronary
syndromes managed with an early invasive strategy : The Acuity trial.
Eurointervention, 2009, 5:115-120.
Hamon M, Coutance G.
Transradial intervention for minimizing bleeding complications in
percutaneous coronary intervention.
Am J Cardiol, 2009, 104(5 Suppl):55C-59C. Review.
Hansmannel F, Lendon C, Pasquier F, Dumont J, Hannequin D,
Chapuis J, Laumet G, Ayral AM, Galimberti D, Scarpini E, Campion D,
Amouyel P, Lambert JC.
Is the ornithine transcarbamylase gene a genetic determinant of
Alzheimer's disease ?
Neurosci Lett, 2009, 449:76-80.
Jolly SS, Amlani S, Hamon M, Yusuf S, Mehta SR.
Radial versus Femoral Access for Coronary Angiography or Intervention
and the Impact on Major Bleeding : A Systematic Review and Metaanalysis of Randomized Trials.
Am Heart J, 2009, 157:132-40.
Goumidi L, Spengler D, Cottel D, Wagner A, Ducimetière P,
Ruidavets JB, Legry V, Arveiler D, Bingham A, Ferrières J,
Amouyel A, Meirhaeghe A.
Study of the genetic variability of ZAC1 (PLAGL1) in French populationbased samples.
J Hypertens, 2009, 27:314-321.
Karvanen J, Silander K, Kee F, Tiret L, Salomaa V, Kuulasmaa K,
Wiklund PG, Virtamo J, Saarela O, Perret C, Perola M, Peltonen L,
Cambien F, Erdmann J, Samani NJ, Schunkert H, Evans A, MORGAM
Project.
The impact of newly identified loci on coronary heart disease, stroke and
total mortality in the MORGAM prospective cohorts.
Genet Epidemiol, 2009, 33:237-246.
Hachulla AL, Launay D, Gaxotte V, de Groote P, Lamblin N, Devos P,
Hatron PY, Beregi JP, Hachulla E.
Cardiac magnetic resonance imaging in systemic sclerosis : a crosssectional observational study of 52 patients.
Ann Rheum Dis, 2009, 68:1878-1884.
Konoshita T, Kato N, Fuchs S, Mizuno S, Aoyama C, Motomura M,
Makino Y, Wakahara S, Inoki I, Miyamori I, Pinet F.
Genetic variant of the renin-angiotensin system and diabetes influences
blood pressure response to angiotensin receptor blocker.
Diabetes care, 2009, 32:1485-1490.
Hachulla E, de Groote P, Gressin V, Sibilia J, Diot E, Carpentier P,
Mouthon L, Hatron PY, Jego P, Allanore Y, Tiev KP, Agard C,
Cosnes A, Cirstea D, Constans J, Farge D, Viallard JF, Harle JR,
Patat F, Imbert B, Kahan A, Cabane J, Clerson P, Guillevin L,
Humbert M ; Itinér AIR-Sclérodermie Study Group.
The three-year incidence of pulmonary arterial hypertension associated
with systemic sclerosis in a multicenter nationwide longitudinal study in
France.
Arthritis Rheum, 2009, 60:1831-1839.
Kotseva K, Wood D, De Backer G, De Bacquer D, Pyörälä K, Keil U ;
EUROASPIRE Study Group.
Cardiovascular prevention guidelines in daily practice : a comparison of
EUROASPIRE I, II, and III surveys in eight European countries.
Lancet, 2009, 373:929-940.
Hachulla E, Bervar JF, Launay D, Lamblin N, Perez T, Mouthon L,
de Groote P, Tillie-Leblond I, Humbert M.
[Dyspnea upon exertion in systemic scleroderma : from symptom to
etiological diagnosis] [Article in French]
Presse Med, 2009, 38:911-926.
Kotseva K, Wood D, Backer GD, Bacquer DD, Pyörälä K, Keil U ;
EUROASPIRE Study Group.
EUROASPIRE III : a survey on the lifestyle, risk factors and use of
cardioprotective drug therapies in coronary patients from 22 European
countries.
Eur J Cardiovasc Prev Rehabil, 2009, 16: 121-137.
117
Contents
Labayen I, Ruiz JR, Vicente-Rodríguez G, Turck D, Rodríguez G,
Meirhaeghe A, Molnár D, Sjöström M, Castillo MJ, Gottrand F,
Moreno LA.
Early life programming of abdominal adiposity in adolescents ; The
HELENA study.
Diabetes Care, 2009, 32:2120-2122.
Mouquet F, Lamblin N, de Groote P.
Indication for bromocriptine in peripartum cardiomyopathy.
Eur J Heart Fail, 2009, 11:223.
Sourgounis A, Lipiecki J, Lo TS, Hamon M.
Coronary stents and chronic anticoagulation.
Circulation 2009; 119:1682-1688.
Lambert JC, Schraen-Maschke S, Richard F, Fievet N, Rouaud O,
Berr C, Dartigues JF, Tzourio C, Alpérovitch A, Buée L, Amouyel P.
Association of plasma amyloid {beta} with risk of dementia : The
prospective Three-City Study.
Neurology, 2009, 73:847-853.
Sparks DL, Hunsaker JC 3rd, Amouyel P, Malafosse A, Bellivier F,
Leboyer M, Courtet P, Helbecque N.
Angiotensin I-converting enzyme I/D polymorphism and suicidal
behaviors.
Am J Med Genet B Neuropsychiatr Genet, 2009, 150B:290-294.
Lambert JC, Heath S, Even G, Campion D, Sleegers K, Hiltunen M,
Combarros O, Zelenika D, Bullido MJ, Tavernier B, Letenneur L,
Bettens K, Berr C, Pasquier F, Fiévet N, Barberger-Gateau P,
Engelborghs S, De Deyn P, Mateo I, Franck A, Helisalmi S, Porcellini E,
Hanon O; the European Alzheimer's Disease Initiative Investigators,
de Pancorbo MM, Lendon C, Dufouil C, Jaillard C, Leveillard T,
Alvarez V, Bosco P, Mancuso M, Panza F, Nacmias B, Bossù P,
Piccardi P, Annoni G, Seripa D, Galimberti D, Hannequin D, Licastro F,
Soininen H, Ritchie K, Blanché H, Dartigues JF, Tzourio C, Gut I,
Van Broeckhoven C, Alpérovitch A, Lathrop M, Amouyel P.
Genome-wide association study identifies variants at CLU and CR1
associated with Alzheimer's disease.
Nat Genet, 2009, 41:1094-1099.
Tilloy E, Montaye M, Kee F, Bingham A, Arveiler D, Ruidavets JB,
Evans A, Haas B, Ferrières J, Ducimetière P, Amouyel P, Dallongeville J.
Contribution of cardiovascular risk factors to coronary risk in patients with
intermittent claudication in the PRIME Cohort Study of European men.
Valgimigli M, Campo G, de Cesare N, Meliga E, Vranckx P, Furgieri A,
Angiolillo DJ, Sabatè M, Hamon M, Repetto A, Colangelo S,
Brugaletta S, Parrinello G, Percoco G, Ferrari R ; Tailoring Treatment
With Tirofiban in Patients Showing Resistance to Aspirin and/or
Resistance to Clopidogrel (3T/2R) Investigators.
Intensifying platelet inhibition with tirofiban in poor responders to
aspirin, clopidogrel, or both agents undergoing elective coronary
intervention: results from the double-blind, prospective, randomized
Tailoring Treatment with Tirofiban in Patients Showing Resistance to
Aspirin and/or Resistance to Clopidogrel study.
Circulation, 2009, 119:3215-3222.
Legry V, Bokor S, Cottel D, Beghin L, Catasta G, Nagy E, GonzalezGross M, Spinneker A, Stehle P, Molnar D, Moreno L, Amouyel P,
Dallongeville J, Meirhaeghe A.
Associations between common genetic polymorphisms in angiopoietinlike proteins 3 and 4 and lipid metabolism and adiposity in European
adolescents and adults.
J Clin Endoc Metab, 2009, 94:5070-5077.
Vereecken C, De Henauw S, Maes L, Moreno L, Manios Y, Phillipp K,
Plada M, De Bourdeaudhuij I ; HELENA Study Group.
Reliability and validity of a healthy diet determinants questionnaire for
adolescents.
Public Health Nutr, 2009, 12:1830-1838.
Legry V, Goumidi L, Huyvaert M, Cottel D, Ferrières J, Arveiler D,
Bingham A, Wagner A, Ruidavets JB, Ducimetière P, Amouyel P,
Meirhaeghe A.
Association study between angiopoietin-like 6 (ANGPTL6) gene
polymorphisms and Metabolic Syndrome-related phenotypes in the
French MONICA Study.
Diabetes Metab, 2009, 35:287-292.
Zerbib J, Seddon JM, Richard F, Reynolds R, Leveziel N, Benlian P,
Borel P, Feingold J, Munnich A, Soubrane G, Kaplan J, Rozet JM,
Souied EH.
rs5888 variant of SCARB1 gene is a possible susceptibility factor for agerelated macular degeneration.
PLoS One, 2009, 4:e7341.
Legry V, Cottel D, Ferrières J, Arveiler D, Andrieux N, Bingham A,
Wagner A, Ruidavets JB, Ducimetière P, Amouyel P, Meirhaeghe A.
Effect of a FTO polymorphism on fat mass, obesity and type 2 diabetes in
the French MONICA Study.
Metabolism, 2009, 58:971-975.
Meroufel D, Médiène-Benchekor S, Dumont J, Benhammamouch S,
Amouyel P, Brousseau T.
Relationship between endothelial nitric oxide synthase gene polymorphisms
and risk of myocardial infarction in the Algerian population.
Egypt J Med Hum Genetics, 2009, 10(1).
Lemesle G, Delhaye C, Sudre A, Broucqsault D, Rosey G, Bauters C,
Lablanche JM.
Impact of high loading and maintenance dose of clopidogrel within the
first 15 days after percutaneous coronary intervention on patient
outcome.
Am Heart J, 2009, 157:375-382.
Book Chapter
Hamon M, Mc Fadden E.
Trans-radial approach for cardiovascular interventions (2nd edition).
ESM Editions 2009.
Meroufel D, Dumont J, Médiène-Benchekor S, Benhammamouch S,
Ducimetière P, Cottel D, Montaye M, Amouyel P, Brousseau T.
Characterisation of arginase 1 gene polymorphisms in the Algerian
population and association with blood pressure.
Clin Biochem, 2009, 42:1178-1182.
2010
Agrinier N, Cournot M, Dallongeville J, Arveiler D, Ducimetière P,
Ruidavets JB, Ferrières J.
Menopause and modifiable coronary heart disease risk factors : A
population based study.
Maturitas, 2010, 65:237-243.
Mouquet F, Cuilleret F, Susen S, Sautière K, Marboeuf P, Ennezat PV,
Mc Fadden EP, Pigny P, Richard F, Hennache B, Vantyghem MC,
Dallongeville J, Jude B, Bertrand ME, Van Belle E.
Metabolic syndrome and collateral vessel formation in patients with
documented occluded coronary arteries : The impact of hyperglycemia,
insulin-resistance, adiponectin and PAI-1.
Eur Heart J, 2009, 30:840-849.
Bauters C, Ennezat PV, Lamblin N, de Groote P.
Left ventricular remodeling and heart failure after myocardial infarction
in elderly patients.
Am J Cardiol, 2010, 105:903-904.
118
Contents
Beseme O, Fertin M, Drobecq H, Amouyel P, Pinet F.
Combinatorial peptide ligand library plasma treatment : Advantages for
accessing low-abundance proteins.
Electrophoresis, 2010, 31:2697-2704.
de Groote P, Lamblin N, Launay D, Bervar JF, Hachulla E. [Screening
and diagnosis of pulmonary arterial hypertension.
Comments regarding the latest guidelines from the European Societies
of Cardiology and of Pulmonology].
Presse Med. 2010; 39 Suppl 1:1S16-21. [French].
Blacher J, Evans A, Arveiler D, Amouyel P, Ferrières J, Bingham A,
Yarnell J, Haas B, Montaye M, Ruidavets JB, Ducimetière P.
Residual cardiovascular risk in treated hypertension and hyperlipidaemia :
the PRIME Study.
J Hum Hypertens, 2010, 24:19-26.
Dubois E, Richard V, Mulder P, Lamblin N, Drobecq H, Henry JP,
Amouyel P, Thuillez C, Bauters C, Pinet F.
Decreased serine207 phosphorylation of troponin T as a biomarker for
left ventricular remodelling after myocardial infarction.
Eur Heart J, 2010, in press.
Bokor S, Legry V, Meirhaeghe A, Ruiz JR, Mauro B, Widhalm K,
Manios Y, Amouyel P, Moreno LA, Molnàr D, Dallongeville J and on
behalf of the HELENA Study group.
Single-nucleotide polymorphism of CD36 locus and obesity in European
adolescents.
Obesity, 2010, 18:1398-1403.
Dumont J, Jossé R, Lambert C, Anthérieu S, Le Hegarat L, Aninat C,
Robin M.A, Guguen-Guillouzo C, Guillouzo A.
Differential toxicity of heterocyclic aromatic amines and their mixture in
metabolically competent HepaRG cells.
Toxicol Appl Pharmacol, 2010, 245:256-263.
Bokor S, Meirhaeghe A, Ruiz JR, Zaccaria M, Widhalm K, Manios Y,
Gonzalez-Gross M, Amouyel P,. Moreno LA, Molnàr D, Dallongeville J,
on behalf of the HELENA Study group.
Common polymorphisms in 6 genes of methyl group metabolism
pathway and obesity in European adolescents.
Int J Pediatr Obes, 2010, in press.
Dupont A, Elkalioubie A, Juthier F, Tagzirt M, Vincentelli A,
Le Tourneau T, Haulon S, Deklunder G, Breyne J, Susen S,
Marechaux S, Pinet F, Jude B.
Frequency of abdominal aortic aneurysm in patients undergoing
coronary artery bypass grafting.
Am J Cardiol, 2010, 105:1545-1548.
Bokor S, Dumont J, Spinneker A, Gonzalez-Gross M, Nova E,
Widhalm K, Moschonis G, Stehle P, Amouyel P, De Henauw S,
Molnar D, Moreno LA, Meirhaeghe A, Dallongeville J.
Single nucleotide polymorphisms in the FADS gene cluster are associated
with delta-5 and delta-6 desaturase activities estimated by serum fatty
acid ratios.
J Lipid Res, 2010, 51:2325-2333.
Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E,
Lowe G, Pepys MB, Thompson SG, Collins R, Danesh J.
C-reactive protein concentration and risk of coronary heart disease,
stroke, and mortality : an individual participant meta-analysis.
Lancet, 2010, 375:132-140.
Emerging Risk Factors Collaboration, Sarwar N, Gao P, Seshasai SR,
Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA,
Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L,
Thompson A, Sattar N, White IR, Ray KK, Danesh J.
Diabetes mellitus, fasting blood glucose concentration, and risk of
vascular disease : a collaborative meta-analysis of 102 prospective studies.
Lancet, 2010, 375:2215-2222.
Canouï-Poitrine F, Luc G, Bard JM, Ferrières J, Yarnell J, Arveiler D,
Morange P, Kee F, Evans A, Amouyel P, Ducimetière P, Empana JP.
Relative contribution of lipids and apolipoproteins to incident Coronary
Heart Disease and Ischemic Stroke : The PRIME Study.
Cerebrovasc Dis, 2010, 30:252-259.
Cohen A, Dallongeville J, Durand-Zaleski I, Bouée S, Le Heuzey JY;
the EPHA Investigators.
Characteristics and management of outpatients with history of or current
atrial fibrillation : The observational French EPHA study.
Empana JP, Jouven X, Canouï-Poitrine F; Luc G, Tafflet M, Haas B,
Arveiler D, Ferrières J, Ruidavets JB; Montaye M, Yarnell J,
Morange P, Kee F, Evans A, Amouyel P, Ducimetière P.
C-Reactive Protein, Interleukin 6, Fibrinogen and risk of sudden death in
European middle-aged men : The PRIME Study.
Arterioscler Thromb Vasc Biol. 2010; 30(10):2047-2052.
Dallongeville J, Dauchet L, de Mouzon O, Réquillart V, Soler L-G.
Increasing fruit and vegetable consumption : a cost-effectiveness analysis
of public policies.
Eur J Public Health, 2010, in press.
Evangelou E, Maraganore DM, Annesi G, Brighina L, Brice A,
Elbaz A, Ferrarese C, Hadjigeorgiou GM, Krueger R, Lambert JC,
Lesage S, Markopoulou K, Mellick GD, Meeus B, Pedersen NL,
Quattrone A, Van Broeckhoven C, Sharma M, Silburn PA, Tan EK,
Wirdefeldt K, Ioannidis JP; for the Genetic Epidemiology of
Parkinson's Disease (GEOPD) Consortium Australia.
Non-replication of association for six polymorphisms from meta-analysis
of genome-wide association studies of Parkinson's disease : Large-scale
collaborative study.
Dallongeville J & Meirhaeghe A.
Triglyceride-mediated pathways and coronary heart disease.
Lancet, 2010, 376:956-957.
Dauchet L, Montaye M, Ruidavets JB, Arveiler D, Kee F, Bingham A,
Ferrières J, Haas B, Evans A, Ducimetière P, Amouyel P, Dallongeville J.
Association between the frequency of fruit and vegetable consumption
and cardiovascular disease in male smokers and non-smokers.
Eur J Clin Nutr, 2010, 64:578-586.
Fertin M, Beseme O, Duban S, Amouyel P, Bauters C, Pinet F.
Deep plasma proteomic analysis of patients with left ventricular
remodeling after a first myocardial infarction.
Proteomics Clin Appl, 2010, in press.
De Bacquer D, Dallongeville J, Kotseva K, Montaye M, Heidrich J,
Wood D, Keil U, De Backer G, EUROASPIRE Study Group.
The challenge facing the care of overweight coronary patients in Europe.
Eur J Cardiovasc Prev Rehabil, 2010, in press.
Gey KF, Ducimetière P, Evans A, Amouyel P, Arveiler D, Ferrières J,
Luc G, Kee F, Bingham A, Yarnell J, Cambien F.
Low plasma retinol predicts coronary events in healthy middle-aged men :
The PRIME Study.
De Bacquer D, Dallongeville J, Heidrich J, Kotseva K, Reiner Z,
Gaita D, Prugger C, Wellmann J, Wood D, De Backer G, Keil U,
on behalf of the EUROASPIRE III Study Group.
Management of overweight and obese patients with coronary heart
disease across Europe.
119
Contents
Goumidi L, Flamant F, Lendon C, Galimberti D, Pasquier F, Scarpini E,
Hannequin D, Campion D, Amouyel P, Lambert JC, Meirhaeghe A.
Study of thyroid hormone receptor alpha gene polymorphisms on
Neurobiol Aging, 2010, in press.
Lambert JC, Sleegers K, González-Pérez A, Ingelsson M,
Beecham GW, Hiltunen M, Combarros O, Bullido MJ, Brouwers N,
Bettens K, Berr C, Pasquier F, Richard F, Dekosky ST, Hannequin D,
Haines JL, Tognoni G, Fiévet N, Dartigues JF, Tzourio C, Engelborghs S,
Arosio B, Coto E, De Deyn P, Del Zompo M, Mateo I, Boada M,
Antunez C, Lopez-Arrieta J, Epelbaum J, Schjeide BM, FrankGarcia A, Giedraitis V, Helisalmi S, Porcellini E, Pilotto A, Forti P,
Ferri R, Delepine M, Zelenika D, Lathrop M, Scarpini E, Siciliano G,
Solfrizzi V, Sorbi S, Spalletta G, Ravaglia G, Valdivieso F, Vepsäläinen S,
Alvarez V, Bosco P, Mancuso M, Panza F, Nacmias B, Bossù P,
Hanon O, Piccardi P, Annoni G, Mann D, Marambaud P, Seripa D,
Galimberti D, Tanzi RE, Bertram L, Lendon C, Lannfelt L, Licastro F,
Campion D, Pericak-Vance MA, Soininen H, Van Broeckhoven C,
Alpérovitch A, Ruiz A, Kamboh MI, Amouyel P.
The CALHM1 P86L polymorphism is a genetic modifier of age at onset in
Alzheimer's Disease: a meta-analysis study.
J Alzheimers Dis, 2010, in press.
Gruson E, Montaye M, Kee F, Wagner A, Bingham A, Ruidavets JB,
Haas B, Evans A, Ferrières J, Ducimetière P, Amouyel P, Dallongeville J.
Anthropometric assessment of abdominal obesity and coronary heart
disease risk in men : the PRIME study.
Heart, 2010, 96:136-140.
Hachulla E, Launay D, Yaici A, Berezne A, de Groote P, Sitbon O,
Mouthon L, Guillevin L, Hatron PY, Simonneau G, Clerson P,
Humbert M; French PAH-SSc Network.
Pulmonary arterial hypertension associated with systemic sclerosis in
patients with functional class II dyspnoea : mild symptoms but severe
outcome.
Lamblin N, Ratajczak P, Hot D, Dubois E, Chwastyniak M, Beseme O,
Drobecq H, Lemoine Y, Koussa M, Pinet F, Amouyel P.
Profile of macrophages in human abdominal aortic aneurysms : a
transcriptomic, proteomic and antibody protein array study.
J Proteome Res, 2010, 9:3720-3729.
Hansmannel F, Sillaire A, Kamboh MI, Lendon C, Pasquier F,
Hannequin D, Laumet G, Mounier A, Ayral A-M, Dekosky ST,
Hauw J-J, Berr C, Mann D, Amouyel P, Campion D, Lambert JC.
Is the urea cycle involved in Alzheimer's disease ?
J Alzheimers Dis, 2010, 21:1013-1021.
Laumet G, Petitprez V, Sillaire A, Ayral AM, Hansmannel F, Chapuis J,
Hannequin D, Pasquier F, Scarpini E, Galimberti D, Lendon C,
Campion D, Amouyel P, Lambert JC.
A study of the association between the ADAM12 and SH3PXD2A
(SH3MD1) genes and Alzheimer's disease.
Neurosci Lett, 2010, 468:1-2.
Hong MG, Alexeyenko A, Lambert JC, Amouyel P, Prince JA.
Genome-wide pathway analysis implicates intracellular transmembrane
protein transport in Alzheimer disease.
J Hum Genet, 2010, in press.
Krüger R, Sharma M, Riess O, Gasser T, Van Broeckhoven C,
Theuns J, Aasly J, Annesi G, Bentivoglio AR, Brice A, Djarmati A,
Elbaz A, Farrer M, Ferrarese C, Gibson JM, Hadjigeorgiou GM,
Hattori N, Ioannidis JP, Jasinska-Myga B, Klein C, Lambert JC,
Lesage S, Lin JJ, Lynch T, Mellick GD, de Nigris F, Opala G,
Prigione A, Quattrone A, Ross OA, Satake W, Silburn PA, Tan EK,
Toda T, Tomiyama H, Wirdefeldt K, Wszolek Z, Xiromerisiou G,
Maraganore DM ; for the Genetic Epidemiology of Parkinson's
disease consortium.
A large-scale genetic association study to evaluate the contribution of
Omi/HtrA2 (PARK13) to Parkinson's disease.
Laumet G, Chouraki V, Grenier Boley B, Legry V, Heath S, Zelenika D,
Fievet N, Hannequin D, Delepine M, Pasquier F, Hanon O, Brice A,
Epelbaum J, Berr C, Dartigues J-F, Tzourio C, Campion D, Lathrop M,
Bertram L, Amouyel P, Lambert JC.
Systematic analysis of candidate genes for Alzheimer’s disease in a
French, genome-wide association study.
J Alzheimers Dis, 2010, 20:1181-1188.
Le Fur I, Laumet G, Richard F, Fievet N, Berr C, Rouaud O, Delcourt C,
Association study of the CFH Y402H polymorphism with Alzheimer's
disease.
Labayen I, Ruiz JR, Meirhaeghe A, Ortega FB, Jiménez-Pavón D,
Castillo MJ, De Henauw S, González-Gross M, Bueno G, Molnar D,
Kafatos A, Esperanza L, Moreno LA.
Association between the FTO rs9939609 polymorphism and leptin in
European adolescents : a possible link with energy balance control. The
HELENA study.
Int J Obes, 2010, in press.
Lemesle G, Sudre A, Bouallal R, Delhaye C, Rosey G, Bauters C,
Lablanche JM.
Impact of thrombus aspiration use and direct stenting on final
myocardial blush score in patients presenting with ST-elevation
myocardial infarction.
Deciphering genetic susceptibility to frontotemporal lobar dementia.
Nat Genet, 2010, 42:189-190.
Lemesle G, Maluenda G, Bonello L, Delhaye C, Sudre A, Bauters C,
Lablanche JM.
Dosing strategies for antiplatelet therapy in percutaneous coronary
intervention.
Hosp Pract (Minneap), 2010, 38:50-58.
Lambert JC, Grenier-Boley B, Chouraki V, Heath S, Zelenika D,
Fievet N, Hannequin D, Pasquier F, Hanon O, Brice A, Epelbaum J,
Berr C, Dartigues J-F, Tzourio C, Campion D, Lathrop M, Amouyel P.
Implication of the immune system in Alzheimer’s disease : evidence from
genome-wide pathway analysis.
J Alzheimers Dis, 2010, 20:1107-1118.
Le Tourneau T, Betto M, Richardson M, Juthier F, Ennezat PV,
Polge AS, Bauters C, Vincentelli A, Deklunder G.
Prospective assessment of multiple cardiac papillary fibroelastomas An
echocardiographic and surgical study.
Int J Cardiol, 2010, in press.
Le Tourneau T, Richardson M, Juthier F, Modine T, Fayad G, Polge AS,
Ennezat PV, Bauters C, Vincentelli A, Deklunder G.
Echocardiography predictors and prognostic value of pulmonary artery
systolic pressure in chronic organic mitral regurgitation.
Heart, 2010, 96:1311-1317.
120
Contents
Leveziel N, Puche N, Richard F, Somner JE, Zerbib J, Bastuji-Garin S,
Cohen S, Korobelnik JF, Sahel JA, Soubrane G, Benlian P, Souied EH.
Genotypic influences on severity of exudative Age-related Macular
Degeneration.
Invest Ophthalmol Vis Sci, 2010, 51:2620-2625.
Sleegers K, Lambert JC, Bertram L, Cruts M, Amouyel P,
Van Broeckhoven C.
The pursuit of susceptibility genes for Alzheimer's disease : progress and
prospects.
Trends Genet, 2010, 26:84-93.
Luc G, Empana JP, Morange P, Juhan-Vague I, Arveiler D, Ferrieres J,
Amouyel P, Evans A, Kee F, Bingham A, Machez E, Ducimetiere P.
Adipocytokines and the risk of coronary heart disease in healthy middle
aged men : the PRIME Study.
Int J Obes (Lond). 2010; 34(1):118-126.
Straczek C, Ducimetiere P, Barberger-Gateau P, Helmer C, Ritchie K,
Jouven X, Carcaillon L, Amouyel P, Tzourio C, Empana JP.
Higher level of systemic C-Reactive Protein is independently predictive of
Coronary Heart Disease in Older Community-Dwelling Adults: the ThreeCity study.
J Am Geriatr Soc, 2010, 58:129-35.
Mekinian A, Lions C, Leleu X, Duhamel A, Lamblin N, Coiteux V,
De Groote P, Hatron PY, Facon T, Beregi JP, Hachulla E, Launay D ;
Lille Amyloidosis Study Group.
Prognosis assessment of cardiac involvement in systemic AL amyloidosis
by magnetic resonance imaging.
Am J Med, 2010, 123:864-868.
Szopa M, Meirhaeghe A, Luan J, Moreno LA, Gonzalez-Gross M,
Vidal-Puig A, Cooper C, Hagen R, Amouyel P, Wareham NJ, Loos RJF.
No association between polymorphisms in the INSIG1 gene and the risk
of type 2 diabetes and related traits.
Am J Clin Nutr, 2010, 92:252-257.
Moliner-Urdiales D, Ruiz JR, Vicente-Rodriguez G, Ortega FB,
Rey-Lopez JP, España-Romero V, Casajús JA, Molnar D, Widhalm K,
Dallongeville J, González-Gross M, Castillo MJ, Sjöström M,
Moreno LA.
Associations of muscular and cardiorespiratory fitness with total and
central body fat in adolescents ; The HELENA Study.
Br J Sports Med, 2010, in press.
Tilloy E, Cottel D, Ruidavets JB, Arveiler D, Ducimetière P,
Bongard V, Haas B, Ferrières J, Wagner A, Bingham A, Amouyel P,
Dallongeville J.
Characteristics of current smokers, former smokers and secondhand
exposure and evolution between 1985 and 2007.
Eur J Cardiovasc Prev Rehabil. 2010, in press.
Triglyceride Coronary Disease Genetics Consortium and Emerging
Risk Factors Collaboration, Sarwar N, Sandhu MS, Ricketts SL,
Butterworth AS, Di Angelantonio E, Boekholdt SM, Ouwehand W,
Watkins H, Samani NJ, Saleheen D, Lawlor D, Reilly MP, Hingorani
AD, Talmud PJ, Danesh J.
Triglyceride-mediated pathways and coronary disease: collaborative
analysis of 101 studies.
Lancet, 2010, 375:1634-1639.
Pigeyre M, Bokor S, Romon M, Gottrand F, Gilbert CC, Valtueña J,
Gómez-Martínez S, Moreno LA, Amouyel P, Dallongeville J,
Meirhaeghe A.
Influence of maternal educational level on the association between the
rs3809508 neuromedin B gene polymorphism and the risk of obesity in
the HELENA study.
Int J Obes (Lond), 2010, 3:478-486.
Plichart M, Barberger-Gateau P, Tzourio C, Amouyel P, Pérès K,
Ritchie K, Jouven X, Ducimetière P, Empana JP.
Disability and incident coronary heart disease in older communitydwelling adults: the Three-City Study.
J Am Geriatr Soc, 2010, 58:636-642.
Van Belle E, Dallongeville J, Vicaut E, Degrandsart A, Baulac C,
Montalescot G, on behalf of The OPERA Investigators.
Ischaemia-modified albumin levels predict long-term outcome in
patients with acute myocardial infarction. The French Nationwide OPERA
study.
Am Heart J, 2010, 159:570-576.
Rodriguez-Artalejo F, Guallar E, Borghi C, Dallongeville J,
De Backer G, Halcox JP, Hernandez-Vecino R, Jimenez FJ, MassoGonzalez EL, Perk J, Steg PG, Banegas JR, Investigators E.
Rationale and methods of the European Study on Cardiovascular Risk
Prevention and Management in Daily Practice (EURIKA).
BMC Public Health, 2010, 10:382.
Vasseur F, Caeyseele T, Barat-Houari M, Lobbens S, Meirhaeghe A,
Meyre D, Froguel P, Amouyel P, Helbecque N.
Concordance of two multiple analytical approaches demonstrate that
interaction between BMI and ADIPOQ haplotypes is a determinant of LDL
cholesterol in a general French population.
J Hum Genet, 2010, 55:227-231.
Ruiz JR, Labayen I, Ortega FB, Legry V, Moreno LA, Dallongeville J,
Martínez-Gómez D, Bokor S, Manios Y, Ciarapica D, Gottrand F,
De Henauw S, Molnar D, Sjöström M, Meirhaeghe A.
Physical activity attenuates the effect of the FTO rs9939609
polymorphism on total and central body fat in adolescents ; The HELENA
Study.
Arch Pediatr Adolesc Med. 2010; 164(4):328-333.
Verier C, Meirhaeghe A, Bokor S, Breidenassel C, Manios, Molnár D,
Artero EG, Nova E, De Henauw S, Moreno LA, Amouyel P, Labayen I,
Bevilacqua N, Turck D, Béghin L, Dallongeville J, Gottrand F.
Breastfeeding modulates the influence of the peroxisome proliferatoractivated receptor gamma (PPARG) Pro12Ala polymorphism on adiposity
in adolescents : the HELENA Cross-Sectional Study.
Diabetes Care, 2010, 33:190-196.
Seshadri S, Fitzpatrick AL, Ikram A, DeStefano AL, Gudnason V,
Boada M, Bis JC, Smith AV, Carassquillo MM, Lambert JC, Harold D,
Schrijvers EMC, Ramirez-Lorca R, Debette S, Longstreth WT,
Janssens CJW,Pankratz, Dartigues J-F, Hollinworth P, Aspelund T,
Hernadez I, Beiser A, Kuller LH, Koudstaal PJ, Dickson DW,
Tzourio C, Abraham R, Antunez C, Du, Y, Rotter JI, Aulchenko YS,
Harris TB, Petersen RC, Berr C, Owen MJ, Lopez-Arrieta J,
Varadarajan BN, Becker JT, Rivadeneira F, Nalls MA, GraffRadford NR, Campion D, Auerbach S, Rice K, Hofman A, Jonsson PV,
Schmidt H, Lathrop M, Mosley TH, Au R, Psaty BM, Uitterlinden AG,
Farrer LA, Lumley T, Ruiz A, Williams J, Amouyel P, Younkin SG,
Wolf PA, Launer LJ, Lopez O, Van Duijn C, Breteler M on behalf of
the Charge, GERAD1 and EADI1 consortia.
Genome-wide association studies of alzheimer’s disease.
JAMA, 2010, 303:1864-65.
Wagner A, Sadoun A, Dallongeville J, Ferrières J, Amouyel P,
Ruidavets JB, Arveiler D.
High blood pressure prevalence and control in a middle-aged French
population and their associated factors : the MONA LISA study.
J Hypertens, 2010, in press.
Zerbib J, Richard F, Puche N, Leveziel N, Cohen SY, Korobelnik JF,
Sahel J, Munnich A, Kaplan J, Rozet JM, Souied EH.
R102G polymorphism of the C3 gene associated with exudative agerelated macular degeneration in a French population.
Mol Vis, 2010, 16:1324-1330.
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Jiménez Pavón D, Ortega FP, Ruiz JR, España Romero V,
García Artero E, Moliner Urdiales D, Gómez Martínez S,
Vicente Rodríguez G, Manios Y, Béghin L, Répasy J, Sjöstrom M,
Moreno LA, González Gross M, Castillo MJ; HELENA Study Group.
Socioeconomic status influences physical fitness in European adolescents
independently of body fat and physical activity : the HELENA study.
Nutr Hosp, 2010, 25:311-316.
Rey-López JP, Vicente-Rodriguez G, Ortega FB, Ruiz JR, MartinezGómez D, De Henauw S, Manios Y, Molnar D, Polito A, Verloigne M,
Castillo MJ, Sjöström M, De Bourdeaudhuij I, Moreno LA ; HELENA
Study Group.
Sedentary patterns and media availability in European adolescents : The
HELENA study.
Prev Med, 2010, 51:50-55.
PhD
Amélie BRUANDET
Directeur de thèse : Philippe Amouyel
« Facteurs pronostiques de patients atteints de démence suivis en centre
mémoire de ressource et de recherche : exemple d'utilisation de bases de
données médicales à des fins de recherche clinique »
Université de Lille 2
23 septembre 2008
Vanessa LEGRY
Directeur de thèse : Aline Meirhaeghe-Hurez
« Recherche de déterminants génétiques des phénotypes associés au
syndrome métabolique en population »
28 septembre 2009
122
Contents
abdominal aortic aneurysms and chronic heart failure. These two
affections are subject to remodelling mechanisms affecting the
cardiovascular system, whose implication in the prognosis of the
patients is critical. Indeed, in consideration of the improved
treatment of the coronary disease and increased life expectancy
of patients, the structural modifications of the cardiovascular
system are now prevailing affecting the prognosis and quality
of life of individuals.
Search for the molecular
determinants of cardiovascular diseases via
proteomic analysis
and candidate gene
approaches
The strategy used consists in comparing the proteome of cells
in patients suffering from these affections to that of cells in nonaffected subjects. Cells used for these comparisons are
macrophages and smooth muscle cells. Bi-dimensional
electrophoresis and protein chips techniques are used.
Significant efforts made to analyse these data using biocomputing before and after these experiments are made. This
approach has already been validated and maps for the
proteome of macrophages (Dupont et al, 2004) and smooth
muscle cells (Dupont et al, 2005), which are critical for the
interpretation of data, were produced by the unit. Our team is
also developing proteomic techniques to increase sensitivity
and be able to analyse proteomes on reduced quantities of
tissues, or even directly on plasma or serum to adjust to the
necessarily limited biological resources of clinical studies in
humans. These experiments have therefore enabled us to
validate the 2D-DIGE Saturation Dye technique applied to
samples collected as part of clinical protocols (Dupont et al,
2008). However, certain proteins having a low molecular weight
(<20 kDa) or hydrophobic proteins that included membrane
proteins cannot be detected by 2-D electrophoresis techniques.
This is why we turned to the use of protein biochips. These
experiments have enabled us to validate the SELDI-TOF
technique to identify differentially expressed proteins having a
low molecular weight. This technique comes in addition to 2D
electrophoresis (Cieniewski-Bernard et al, 2008).
Florence PINET
DR 2 Inserm
Group Members :
Bauters Christophe, PU PH Lille 2
Degroote Pascal, PU CHRU Lille
Hamon Martial, PU-PH CHU Caen
Huygens Maggy, Technician IPL
Beseme Olivia, Engineer Lille 2
Acosta Adélina, Postdoctoral fellow
Dubois Emilie, Postdoctoral fellow
Boytard Ludovic, PhD Student Lille 2
Fertin Marie, PhD Student Lille 2
Burdese Justine, Master 2 Paris VII
Key words :
Differential proteomics. Bioinformatics. Biomarkers. Cardiovascular diseases (coronary heart disease, aneurysm, heart
failure). Risk factors. Translational research.
In the past thirty years, more than 200 cardiovascular disease
risk factors have been identified including approximately ten
modifiable risk factors - which seem to account for the major
part of avoidable cases in a population. However, considering
their interactions with each other, their impact on the
individual risk varies significantly. The determinants for these
variations are difficult to assess and are often related to
individual susceptibilities.
These various techniques are then applied to clinical studies
developed with cardiologists. These studies have been
designed to maximise differences between cases and. So, the
LILAS protocol is a case-control study which included 24 men
suffering from abdominal aortic aneurysms of atherosclerotic
origin first treated using surgery and 21 men affected by
obliterating peripheral arteriopathy treated by surgery
though with no abdominal aortic aneurysms. For each
subject, we preserve serum, and isolate macrophages and
smooth muscle cells with an explant of a fragment of the
vascular segment obtained after surgical excision. We have
also finalised the REVE study whose primary objective is to
identify new determinants for post-infarction left ventricular
remodelling. Patients included had to have suffered from an
inaugural myocardial infarction of anterior topography; they
were regularly examined using cardiac echography – the first
time 7 days after, the 2nd time 3 months after and the last
time during examinations performed after 1 year. REVE-1
findings showed that, unfortunately, left ventricular
remodelling still remained a relatively frequent development
(affecting one third of all patients followed-up in the REVE-1
study) (Savoye et al, 2006). In the REVE 1 study, we developed
experimental conditions on the basis of 4 control samples
and 4 patients’ samples on 3 types of chips - hydrophobic
(H50), anionic (Q10) and cationic (CM10) chips. The sample of
REVE (n=93) was divided into tertiles and we compared
samples from tertile 1 (n=31) (non-remodelling patients) with
These individual susceptibilities are analysed using candidate
gene approaches. This is how, for heart failure - a condition
whose prognosis still is severe - we have studied the association
of various functional polymorphisms of physiopathological
pathways involved in its development or prognosis. We were
therefore able to show, in a clinical series of more than 1,200
patients suffering from heart failure (one of the largest cohorts
on the genetics of heart failure developed with the cardiologists
of the CHRU of Lille), the prognosis role of polymorphisms in
metalloproteases 3 and 9 genes (Mizon-Gérard et al, 2004) and
the absence of any association with the polymorphisms of the
genes coding beta-adrenergic receptors (de Groote et al, 2005)
or AMDP1 (de Groote et al, 2007). In addition to genetic
polymorphisms, we have also shown the relevance of two
biochemical markers (Lamblin et al, 2005a & 2005b).
In order to identify further markers for these risk variations, we
have developed a strategy for the search of original susceptibility
genes on the basis of differential proteomic analyses. Our close
cooperation with cardiologists and their active involvement in
research efforts conducted in the laboratory have enabled us to
set up clinical studies to collect biological samples adapted to
these approaches. Two specific pathological fields were selected:
123
Contents
Bauters C, Ennezat PV, Tricot O, Lauwerier B, Lallemant R,
Saadouni H, Quandalle P, Jaboureck O, Lamblin N, Le Tourneau T ;
on behalf of The REVE Investigators.
Stress hyperglycaemia is an independent predictor of left ventricular
remodeling after first anterior myocardial infarction in non-diabetic patients.
Eur Heart J, 2007, 28:546-552.
Bauters A, Ennezat PV, Tricot O, Lallemant R, Aumegeat V,
Segrestin B, Quandalle P, Lamblin N, Bauters C ; REVE Investigators.
Relation of admission white blood cell count to left ventricular
remodeling after anterior wall acute myocardial infarction.
Am J Cardiol, 2007, 100:182-184.
samples from tertile 3 (n=31) (patients having left ventricular
remodelling exceeding 20%). We have found 4 differentially
expressed peaks. We have developed elution conditions for
each peak to be able to identify them using MALDI-TOF and
LC/MS-MS. Three peaks correspond to one protein and one
to another. We confirmed the identification of peaks through
the immuno-depletion of patients’ plasma using specific
antibodies. We were able to evidence that differences in the
expression of all 3 peaks corresponded to post-translational
variants of chain α1 of haptoglobin and the other to
hemoglobin (Pinet et al, 2008).
Brasselet C, Tassan S, Nazeyrollas P, Hamon M, Metz D.
Randomized comparison of femoral versus radial approach for
percutaneous coronary intervention using abxicimab in acute
myocardial infarction : Results of the FARMI (Five french Arterial access
with Reopro in Myocardial Infarction) Trial.
Heart, 2007, 93:1556-1561.
Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ,
van Es G-A, Steg PG, Morel M-A, Mauri L, Vranckx P, McFadden E,
Lansky A, Hamon M, Krucoff MW, Serruys PW.
Clinical endpoints in coronary stent trials. A case for standardized definitions.
Circulation, 2007, 115:2344-2351.
Finally, in order to limit variability and to have more protein
material, we applied our techniques to an animal model
(LREVMODEL study). This is a heart failure experimental model
obtained in rats by ligaturing the coronary artery, developed in
cooperation with Dr V Richard, Dr P Mulder and Pr C Thuillez at
INSERM in Rouen, France. The first part of the differential
proteomic analysis was made on blood and heart tissue samples
2 months after ligaturing. Concerning the analysis of the left
ventricle, using 2D electrophoresis, we highlighted 49
differentially expressed polypeptidic spots between the left
ventricle (LV) of HF rats and controls. We have identified 27
different proteins involved in oxidative stress and proteasomal
degradation pathways, energetic metabolism with, among other
things, an increased expression of glycolytic enzymes and
reduced expression of proteins involved in the degradation
pathway of fatty acids or molecular chaperones, including HSP’s,
as well as proteins involved in the kinin pathway. This was how
we were able to show that proteins involved in oxidative stress
were modulated differently in the early and late phases of left
ventricular remodelling and differently depending on the severity of heart failure (Cieniewski-Bernard et al, review underway).
Debette S, Bauters C, Leys D, Lamblin N, Pasquier F, de Groote P.
Prevalence and determinants of cognitive impairment in chronic heart
failure patients.
Congest Heart Fail, 2007, 13(4):205-208.
de Groote P, Mouquet F, Dallongeville J, Lamblin N, Bauters C.
The impact of the AMPD1 gene polymorphism on exercise capacity, other
prognostic parameters, and survival in patients with stable congestive
heart failure. A study on 686 consecutive patients.
Am Heart J, 2007, 153:e15. [Letter to the editor.]
de Groote P, Delour P, Mouquet F, Lamblin N, Dagorn J, Hennebert O,
Le Tourneau T, Foucher-Hossein C, Verkindère C, Bauters C.
The effects of beta-blockers in patients with stable chronic heart failure.
Predictors of left ventricular ejection fraction improvement and impact on
prognosis.
Am Heart J, 2007, 154:589-595.
de Groote P, Ennezat PV, Mouquet F.
Bisoprolol in the treatment of chronic heart failure.
Vasc Health Risk Manag, 2007, 3:431-439.
After these new known or unknown proteins were determined,
we tried to go back to the gene and search for polymorphisms.
The new potential genetic susceptibility factors so identified
were then tested in the epidemiological studies defined in team
1 on the vascular risk and in studies used by team 3 on the
neurodegenerative risk. Transcriptome analyses using tailormade chips were also carried out and a DNA chip was made to
incorporate known genes suspected of being involved in
remodelling (family of metalloproteases).
de Groote P, Isnard R, Assyag P, Clersson P, Ducardonnet A,
Galinier M, Jondeau G, Leurs I, Thébaut JF, Komajda M.
Is the gap between guidelines and clinical practice in heart failure
treatment being filled ? Insights from the IPACT RECO survey.
Eur J Heart Fail, 2007, 9:1205-1211.
Dumont J, Zureik M, Bauters C, Grupposo MC, Cottel D, Montaye M,
Hamon M, Ducimetière P, Amouyel P, Brousseau T.
Association of OAZ1 Gene Polymorphisms With Subclinical and Clinical
Vascular Events.
Publications
Ennezat PV, Gonin X, Darchis J, de Groote P, Lamblin N, Bauters C,
Lejemtel T, Asseman P.
Delayed recovery of left ventricular systolic dysfunction : ''give time to
medical therapy''.
Minerva Cardioangiol, 2007, 55:426-427.
2007
Bauters C, Lamblin N, Ennezat PV, Mycinski C, Tricot O, Nugue O,
Segrestin B, Hannebicque G, Agraou B, Polge AS, de Groote P,
Helbecque N, Amouyel P; REVE Investigators.
A prospective evaluation of left ventricular remodeling after inaugural
anterior myocardial infarction as a function of gene polymorphisms in the
renin-angiotensin-aldosterone, adrenergic, and metalloproteinase systems.
Am Heart J. 2007; 153:641-648.
Hamon M, Gomes S, Clergeau M-R, Fradin S, Morello R, Hamon M.
Risk of Acute Brain Injury Related to Cerebral Microembolism During
Cardiac Catheterization Performed by Right Upper Limb Arterial Access.
Stroke, 2007, 2176-2179.
124
Contents
Hamon M, Burzotta F, Oppenheim C, Morello R, Viader F, Hamon M.
Silent Cerebral Infarct After Cardiac Catheterization as Detected by
Diffusion Weighted Magnetic Resonnance Imaging : A Randomized
Comparison of Radial and Femoral arterial approaches.
Trials, 2007, 8:15.
Valgimigli M, Bolognese L, Anselmi M, Campo G, Rodriguez AE, de
Cesare N, Cohen DJ, Sheiban I, Colangelo S, Pasquetto G, Hamon M,
Vranckx P, Ferrario M, Prati F, Agostoni P, Malagutti P, Arcozzi C,
Parrinello G, Vassanelli C, Ferrari R, Percoco G.
Two-by-two factorial comparison of high-bolus-dose tirofiban followed by
standard infusion versus abciximab and sirolimus-eluting versus baremetal stent implantation in patients with acute myocardial infarction:
Design and rationale for the MULTI-STRATEGY trial.
Am Heart J, 2007, 154:39-45.
Hamon M, Morello R, Riddell JW, Hamon M.
Coronary arteries : Diagnostic performance of 16- versus 64-slice spiral
computed tomography of coronary arteries as compared to invasive
coronary angiography : Meta-analysis.
Radiology, 2007, 245:720-731.
de Groote P.
Cardiologies et maladies vasculaires. Indications thérapeutiques.
Masson, Paris, 2007, pages 719-722.
Komajda M, Amouyel P, Johnson N, Bergougnoux L, Laperche T,
de Groote P, Jaillon P, Cohen-Solal A ; Comité scientifique d'étude
de KEOPS et des investigateurs.
Treating heart failure with carvedilol in private practice (initiating
treatment and follow-up at one year). The KEOPS study.
Arch Mal Coeur Vaiss, 2007, 100:818-826.
de Groote P.
Cardiologies et maladies vasculaires. Cœurs et maladies systémiques
auto-immunes.
Masson, Paris, 2007, pages 1209-1223.
Launay D, Lambert M, Hachulla E, de Groote P, Remy-Jardin M,
Queyrel V, Morell-Dubois S, Charlanne H, Cortot A, Hatron PY.
Entéropathie exsudative révélant une péricardite chronique constrictive
idiopathique.
Rev Med Interne, 2007, 28:38-41.
de Groote P.
Traité de médecine cardiovasculaire du sujet âgé. Utilisation des dérivés
nitrés et médicaments apparentés.
Médecine-Sciences, Flammarion, Paris 2007, pages 510-514.
de Groote P.
Cardiologie et pathologies vasculaires. L’insuffisance cardiaque.
Med-Line Editions, Paris 2007, pages 261-284.
Le Hello C, Morello R, Lequerrec A, Duarte C, Riddell J, Hamon M.
Effect of PlA1/A2 glycoprotein IIIa gene polymorphism on the long-term
outcome after successful coronary stenting.
Thrombosis Journal, 2007, 5:19.
Dupont A, Pinet F.
The proteome and secretome of human arterial smooth muscle cell.
Methods Mol Biol, 2007, 357:225-233.
Manoukian SV, Feit F, Mehran R, Voeltz MD, Ebrahimi R, Hamon M,
Dangas GD, Lincoff AM, White HD, Moses JW, King SB 3rd,
Ohman EM, Stone GW.
Impact of major bleeding on 30-day mortality and clinical outcomes in
patients with acute coronary syndromes : an analysis from the ACUITY Trial.
J Am Coll Cardiol, 2007, 49:1362-1368.
Pinet F.
Isolation and analysis of renal vessels.
In : Renal and urinary Proteomics, Ed. Thongboonkerd, Wiley. 2007.
2008
Maréchaux S, Ennezat PV, Lejemtel TH, Polge AS, de Groote P,
Asseman P, Nevière R, Le Tourneau T, Deklunder G.
Left ventricular response to exercise in aortic stenosis: an exercise
echocardiographic study.
Echocardiography, 2007, 24:955-959.
Agostini D, Verberne HJ, Hamon M, Jacobson AF, Manrique A.
Cardiac (123)I-MIBG scintigraphy in heart failure.
Q J Nucl Med Mol Imaging, 2008, 52:369-377.
Bauters C.
Silent coronary plaque rupture.
Marquié C, Duchemin A, Klug D, Lamblin N, Mizon F, Cordova H,
Boulo M, Lacroix D, Pol A, Kacet S.
Can we implant cardioverter defibrillator under minimal sedation ?
Europace 2007, 9:545-550.
Bauters C.
Pathophysiology of coronary artery disease.
Rev Prat, 2008, 58:1523-1526.
Meirhaeghe A, Sandhu MS, McCarthy MI, de Groote P, Cottel D,
Arveiler D, Ferrières J, Groves CJ, Hattersley AT, Hitman GA,
Walker M, Wareham NJ, Amouyel P.
Association between the T-381C polymorphism of the brain natriuretic
peptide gene and risk of type 2 diabetes in human populations.
Hum Mol Genet, 2007, 16:1343-1350.
Bauters C, Lamblin N, de Groote P.
High-sensitivity C-reactive protein for risk stratification in patients with
heart failure.
Am Heart J, 2008 Feb, 155:e7.
Riddell JW, Chiche L, Plaud B, Hamon M.
Coronary stents and noncardiac surgery.
Circulation, 2007, 116:e378-e382.
Burzotta F, Trani C, Hamon M, Amoroso G, Kiemeneij F.
Transradial approach for coronary angiography and interventions in
patients with bypass grafts : tips and tricks.
Cath Cardiovasc Interv, 2008, 72: 263-72.
Schmidt J, Launay D, Soudan B, Hachulla E, de Groote P, Lambert M,
Queyrel V, Morell-Dubois S, Hatron PY.
Intérêt du dosage plasmatique de l’endothéline au cours de la
sclérodermie systémique.
Rev Med Interne, 2007, 28:371-376.
Cieniewski-Bernard C, Mulder P, Henry JP, Drobecq H, Dubois E,
Pottiez G, Thuillez C, Amouyel P, Richard V, Pinet F.
Proteomic analysis of left ventricular remodelling in an experimental
model of heart failure.
J Proteome Res, 2008, 7:5004-5016.
Cieniewski-Bernard C, Acosta A, Dubois E, Lamblin N, Beseme O,
Chwastyniak M, Amouyel P, Bauters C, Pinet F.
Proteomic analysis in cardiovascular diseases.
Clin Exp Pharmacol Physiol, 2008, 35:362-366.
125
Contents
Clergeau MR, Morello R, Le Page O, Hamon M.
Intérêt des statines dans la prévention des infarctus post-angioplastie
coronaire. Revue systématique et méta-analyse.
Ann Cardiol Ang, 2008, 57:181-186.
Hamon M, Baron J-C, Viader F, Hamon M.
Periprocedural stroke and cardiac catheterization.
Circulation, 2008, 118: 678-683.
Hamon M, Champ-Rigot L, Morello R, Riddell JW, Hamon M.
Diagnostic accuracy of in-stent coronary restenosis detection with
multislice spiral computed tomography: a meta-analysis.
Eur Radiol, 2008, 18:217-225.
Coutance G, Le Page O, Lo T, Hamon M.
Prognostic value of Brain Natriuretic Peptide in acute pulmonary embolism.
Critical Care, 2008, 12:R109.
de Groote P, Herpin D, Diévart F, Hanon O, Trochu JN, Artigou JY,
Galinier M, Habib G, Juillière Y, Neuder Y, Roudaut R, Komajda M.
Treatment of heart failure with preserved systolic function.
Hamon M, Lepage O, Malagutti P, Riddell JW, Morello R, Agostini D,
Hamon M.
Diagnostic performance of 16- and 64-section spiral CT for coronary
artery bypass graft assessment : Meta-analysis.
Radiology, 2008, 247:679-686.
de Groote P, Lamblin N, Mouquet F, Bauters C.
No gender survival difference in a population of patients with chronic heart
failure related to left ventricular systolic dysfunction and receiving optimal
medical therapy.
Hamon M, Nolan J.
Should radial artery access be the gold standard for PCI ?
Heart, 2008, 94:1530-1532.
Lemesle G, Sudre A, Modine T, Delhaye C, Rosey G, Gourlay T,
Bauters C, Lablanche JM.
High incidence of recurrent in stent thrombosis after successful treatment
of a first in stent thrombosis.
Catheter Cardiovasc Interv, 2008, 72:470-478.
de Groote P, Gressin V, Hachulla E, Carpentier P, Guillevin L, Kahan A,
Cabane J, Francès C, Lamblin N, Diot E, Patat F, Sibilia J, Petit H,
Cracowski JL, Clerson P, Humbert M ; ItinerAIR-Scleroderma Investigators.
Evaluation of cardiac abnormalities by Doppler echocardiography in a
large nationwide multicentric cohort of patients with systemic sclerosis.
Ann Rheum Dis, 2008, 67:31-36.
Le Tourneau T, Susen S, Caron C, Millaire A, Maréchaux S, Polge AS,
Vincentelli A, Mouquet F, Ennezat PV, Lamblin N, de Groote P,
Van Belle E, Deklunder G, Goudemand J, Bauters C, Jude B.
Functional impairment of von Willebrand factor in hypertrophic
cardiomyopathy: relation to rest and exercise obstruction.
Circulation, 2008, 118:1550-1557.
Dupont A, Chwastyniak M, Beseme O, Guihot AL, Drobecq H,
Amouyel P, Pinet F.
Application of saturation dye 2D-DIGE proteomics to characterize
proteins modulated by oxidized low density lipoprotein treatment of
human macrophages.
J Proteome Res, 2008, 7:3572-3582.
Lo T, Sourgounis A, Nolan J, Hamon M.
Starting a transradial programme : How to go about it ?
Ind Heart J, 2008, 60 (Suppl A):A3-A8.
Ennezat PV, Maréchaux S, Huerre C, Deklunder G, Asseman P, Jude B,
Van Belle E, Mouquet F, Bauters C, Lamblin N, Lejemtel TH, de Groote P.
Exercise does not enhance the prognostic value of Doppler
echocardiography in patients with left ventricular systolic dysfunction
and functional mitral regurgitation at rest.
Am Heart J, 2008, 155:752-757.
Maillard-Lefebvre H, Launay D, Mouquet F, Gaxotte V, Hachulla E,
de Groote P, Lambert M, Queyrel V, Morell-Dubois S, Bérégi JP,
Bauters C, Hatron PY.
Polyarteritis nodosa-related coronary aneurysms.
J Rheumatol, 2008, 35:933-934.
Ennezat PV, Darchis J, Lamblin N, Tricot O, Elkohen M, Aumégeat V,
Equine O, Dujardin X, Saadouni H, Le Tourneau T, de Groote P,
Bauters C ; REVE Investigators.
Left ventricular remodeling is associated with the severity of mitral
regurgitation after inaugural anterior myocardial infarction--optimal
timing for echocardiographic imaging.
Am Heart J, 2008, 155:959-965.
Maréchaux S, Pinçon C, Le Tourneau T, de Groote P, Huerre C, Asseman P,
Van Belle E, Nevière R, Bauters C, Deklunder G, Lejemtel TH, Ennezat PV.
Cardiac correlates of exercise induced pulmonary hypertension in patients
with chronic heart failure due to left ventricular systolic dysfunction.
Echocardiography, 2008, 25:386-393.
Mouquet F, Lions C, de Groote P, Bouabdallaoui N, Willoteaux S,
Dagorn J, Deruelle P, Lamblin N, Bauters C, Beregi JP.
Characterisation of peripartum cardiomyopathy by cardiac magnetic
resonance imaging.
Eur Radiol, 2008, 18:2765-2769.
Ennezat PV, Lamblin N, Mouquet F, Tricot O, Quandalle P, Aumégeat V,
Equine O, Nugue O, Segrestin B, de Groote P, Bauters C ; REVE
Investigators.
The effect of ageing on cardiac remodelling and hospitalization for heart
failure after an inaugural anterior myocardial infarction.
Eur Heart J, 2008, 29:1992-1999.
Pinet F, Beseme O, Cieniewski-Bernard C, Drobecq H, Jourdain S,
Lamblin N, Amouyel P, Bauters C.
Predicting left ventricular remodeling after a first myocardial infarction
by plasma proteome analysis.
Proteomics, 2008, 8:1798-1808.
Ennezat PV, Lefetz Y, Maréchaux S, Six-Carpentier M, Deklunder G,
Montaigne D, Bauchart JJ, Mounier-Véhier C, Jude B, Nevière R,
Bauters C, Asseman P, de Groote P, Lejemtel TH.
Left ventricular abnormal response during dynamic exercise in patients
with heart failure and preserved left ventricular ejection fraction at rest.
J Card Fail, 2008, 14:475-480.
Richardson-Lobbedez M, Maréchaux S, Bauters C, Darchis J,
Auffray JL, Bauchart JJ, Aubert JM, Lejemtel TH, Lesenne M,
Van Belle E, Goldstein P, Asseman P, Ennezat PV.
Prognostic importance of tissue Doppler-derived diastolic function in patients
presenting with acute coronary syndrome : a bedside echocardiographic study.
Eur J Echocardiogr, 2008, 9:594-598.
Hamon M, Agostini D, Le Page O, Riddell JW, Hamon M.
Prognostic impact of right ventricular involvement in patients with acute
myocardial infarction. meta-analysis.
Critical Care Med, 2008, 36:2023-2033.
Ritz MF, Ratajczak P, Curin Y, Cam E, Mendelowitsch A, Pinet F,
Andriantsitohaina R.
Chronic treatment with red wine polyphenol compounds mediates
neuroprotection in a rat model of ischemic cerebral stroke.
J Nutr, 2008, 138:519-525.
Hamon M, Sourgounis A.
Radiation exposure and vascular access site.
Eur Heart J, 2008, 29:954.
126
Contents
Hamon M, Rasmussen LH, Manoukian SV, Cequier A, Lincoff AM,
Rupprecht HJ, Gersh BJ, Mann T, Bertrand ME, Mehran R, Stone GW.
Choice of arterial access site and outcomes in patients with acute coronary
syndromes managed with an early invasive strategy : The Acuity trial.
Eurointervention, 2009, 5:115-120.
Valgimigli M, Campo G, de Cesare N, Vranckx P, Hamon M,
Angiolillo D, Sabat M, Ferrari F, Tumscitz C, Repetto A, Meliga E,
Kubbajeh M, Benassi A, Parrinello G, Percoco G, Ferrari R.
Tailoring Treatment with Tirofiban in patients showing Resistance to
aspirin and/or Resistance to clopidogrel (3T/2R) study. Rationale for the
Study and Protocol Design.
Cardiovasc Drugs Ther, 2008, 4:313-320.
Hamon M, Coutance G.
Transradial intervention for minimizing bleeding complications in
percutaneous coronary intervention.
Am J Cardiol. 2009; 104(5 Suppl):55C-59C. Review.
2009
Acosta-Martin AE, Chwastyniak M, Beseme O, Drobecq H,
Amouyel P, Pinet F.
Impact of incomplete DNase I treatment on human macrophage analysis.
Proteomics Clin Appl, 2009, 3:1-11.
Jolly SS, Amlani S, Hamon M, Yusuf S, Mehta SR.
Radial versus Femoral Access for Coronary Angiography or Intervention
and the Impact on Major Bleeding : A Systematic Review and Metaanalysis of Randomized Trials.
Am Heart J, 2009, 157:132-140.
Allouch M, Zhong YZ, Riddell JW, Sabatier R, Hamon M.
Transradial coronary rotational atherectomy using 5-French guiding
catheters.
Chin Med J. (Engl), 2009, 122:1356-1358.
Konoshita T, Kato N, Fuchs S, Mizuno S, Aoyama C, Motomura M,
Makino Y, Wakahara S, Inoki I, Miyamori I, Pinet F.
Genetic variant of the renin-angiotensin system and diabetes influences
blood pressure response to angiotensin receptor blocker.
Diabetes care, 2009, 32:1485-1490.
Clergeau M-R, Hamon M, Morello R, Saloux E, Viader F, Hamon M.
Silent cerebral infarcts in patients with pulmonary embolism and a patent
foramen ovale : a prospective diffusion-weighted magnetic resonnance
imaging study.
Stroke, 2009, 40:3758-3762.
Lemesle G, Delhaye C, Sudre A, Broucqsault D, Rosey G, Bauters C,
Lablanche JM.
Impact of high loading and maintenance dose of clopidogrel within the
first 15 days after percutaneous coronary intervention on patient outcome.
Am Heart J, 2009, 157:375-382.
Delhaye C, Sudre A, Lemesle G, Maréchaux S, Broucqsault D,
Hennache B, Bauters C, Lablanche JM.
Preprocedural high-sensitivity C-reactive protein predicts death or
myocardial infarction but not target vessel revascularization or stent
thrombosis after percutaneous coronary intervention.
Le Tourneau T, Betto M, Richardson M, Juthier F, Ennezat PV, Polge
AS, Bauters C, Vincentelli A, Deklunder G.
Prospective assessment of multiple cardiac paillary fibroelastomas. An
echocardiographic and surgical study.
Int J Cardiol, 2009, Dec 22. [Epub ahead of print]
Am J Hypertens, 2009, 22:993-1000.
Mouquet F, Lamblin N, de Groote P.
Indication for bromocriptine in peripartum cardiomyopathy.
Eur J Heart Fail, 2009, 11:223.
Sourgounis A, Lipiecki J, Lo TS, Hamon M.
Coronary stents and chronic anticoagulation.
Circulation, 2009, 119:1682-1688.
Hachulla AL, Launay D, Gaxotte V, de Groote P, Lamblin N, Devos P,
Hatron PY, Beregi JP, Hachulla E.
Cardiac magnetic resonance imaging in systemic sclerosis : a cross-sectional
observational study of 52 patients.
Ann Rheum Dis, 2009, 68:1878-1884.
Valgimigli M, Campo G, de Cesare N, Meliga E, Vranckx P, Furgieri A,
Angiolillo DJ, Sabatè M, Hamon M, Repetto A, Colangelo S,
Brugaletta S, Parrinello G, Percoco G, Ferrari R ; Tailoring Treatment
With Tirofiban in Patients Showing Resistance to Aspirin and/or
Resistance to Clopidogrel (3T/2R) Investigators.
Intensifying platelet inhibition with tirofiban in poor responders to
aspirin, clopidogrel, or both agents undergoing elective coronary
intervention: results from the double-blind, prospective, randomized
Tailoring Treatment with Tirofiban in Patients Showing Resistance to
Aspirin and/or Resistance to Clopidogrel study.
Circulation, 2009, 119:3215-3222.
Hachulla E, de Groote P, Gressin V, Sibilia J, Diot E, Carpentier P,
Mouthon L, Hatron PY, Jego P, Allanore Y, Tiev KP, Agard C,
Cosnes A, Cirstea D, Constans J, Farge D, Viallard JF, Harle JR,
Patat F, Imbert B, Kahan A, Cabane J, Clerson P, Guillevin L,
Humbert M ; Itinér AIR-Sclérodermie Study Group.
The three-year incidence of pulmonary arterial hypertension associated with
systemic sclerosis in a multicenter nationwide longitudinal study in France.
Arthritis Rheum, 2009, 60:1831-1839.
Hamon M, Mc Fadden E.
Trans-radial approach for cardiovascular interventions (2nd edition).
ESM Editions 2009.
Hachulla E, Bervar JF, Launay D, Lamblin N, Perez T, Mouthon L,
de Groote P, Tillie-Leblond I, Humbert M.
[Dyspnea upon exertion in systemic scleroderma : from symptom to
etiological diagnosis] [Article in French]
Presse Med, 2009, 38:911-926.
2010
Bauters C, Ennezat PV, Lamblin N, de Groote P.
Left ventricular remodeling and heart failure after myocardial infarction
in elderly patients.
Am J Cardiol, 2010, 105:903-904.
Hachulla E, Carpentier P, Gressin V, Diot E, Allanore Y, Sibilia J,
Launay D, Mouthon L, Jego P, Cabane J, de Groote P, Chabrol A,
Lazareth I, Guillevin L, Clerson P, Humbert M ; ItinérAIRSclérodermie Study Investigators.
Risk factors for death and the 3-year survival of patients with systemic
sclerosis: the French ItinérAIR-Sclérodermie study.
Beseme O, Fertin M, Drobecq H, Amouyel P, Pinet F.
Combinatorial peptide ligand library plasma treatment : advantages for
accessing low-abundance proteins.
Electrophoresis, 2010, 31:2697-2704.
127
Contents
Dubois E, Richard V, Mulder P, Lamblin N, Drobecq H, Henry JP,
Amouyel P, Thuillez C, Bauters C, Pinet F.
Decreased Serine207-phosphorylated of troponin T as a biomarker for
left ventricular remodeling after myocardial infarction.
Eur Heart J, 2010, Apr 25. [Epub ahead of print].
Patent
Pinet F, Richard V, Bauters C, Mulder P
Post-translation modified cardiac troponin T as a biomarker of a risk for
heart failure.
EPO9305471.6 du 22 mai 2009
PCT/EP2010/056931 du 20 Mai 2010
Inserm / Institut Pasteur de Lille
Dupont A, Elkalioubie A, Juthier F, Tagzit M, Vincentelli A,
Le Tourneau T, Haulon S, Deklunder G, Breyne J, Susen S,
Marechaux S, Pinet F, Jude B.
Frequency of abdominal aortic aneurysm in patients undergoing
coronary artery bypass grafting.
Am. J Cardiol, 2010, 105:1545-1548.
Fertin M, Beseme O, Duban S, Amouyel P, Bauters C, Pinet F.
Deep plasma proteomic analysis of patients with left ventricular
remodeling after a first myocardial infarction.
Proteomics Clin Appl, 2010a, 4:654-673.
Fertin M, Hennache B, Hamon M, Biausque F, Elkohen M, Nugue O,
Ennezat PV, Tricot O, Lamblin N, Pinet F, Bauters C.
Usefulness of serial assessment of B-type natriuretic peptide, troponin I,
and C-reactive protein to predict left ventricular remodeling after acute
myocardial infarction (From the REVE-2 study).
Am J Cardiol, 2010b, in press.
Lamblin N, Ratajczak P, Hot D, Dubois E, Chwastyniak M, Beseme O,
Drobecq H, Lemoine Y, Koussa M, Amouyel P, Pinet F.
Profile of macrophages in human abdominal aortic aneurysms : a
transcriptomic, proteomic and protein array study.
J Prot Res, 2010, 9:3720-3725.
Lemesle G, Sudre A, Bouallal R, Delhaye C, Rosey G, Bauters C,
Lablanche JM.
Impact of thrombus aspiration use and direct stenting on final
myocardial blush score in patients presenting with ST-elevation
myocardial infarction.
Le Tourneau T, Richardson M, Juthier F, Modine T, Fayad G, Polge AS,
Ennezat PV, Bauters C, Vincentelli A, Deklunder G.
Echocardiography predictors and prognostic value of pulmonary artery
systolic pressure in chronic organic mitral regurgiation.
Heart, 2010, 96:1311-1317.
Mekinian A, Lions C, Leleu X, Duhamel A, Lamblin N, Coiteux V,
De Groote P, Hatron PY, Facon T, Beregi JP, Hachulla E, Launay D ;
Lille Amyloidosis Study Group.
Prognosis assessment of cardiac involvement in systemic AL amyloidosis
by magnetic resonance imaging.
Am J Med, 2010, 123(9):864-868
PhD
Adelina Elena ACOSTA MARTIN
Directeur de thèse Florence Pinet
« Recherche de biomarqueurs de l'anévrysme de l'aorte abdominale »
14 décembre 2009
Emilie DUBOIS
Directeur de thèse Christophe Bauters
« Etude de la phosphorylation lors du remodelage ventriculaire postinfarctus dans un modèle expérimental d’insuffisance cardiaque »
18 octobre 2010
128
Contents
However, the discovery of new candidate genes in
dementias still is complex and many results derived from
association studies could not be replicated. In order to
improve our probability of identifying relevant candidate
genes, we combined to our genetic epidemiological
approach an analysis of the variations in gene expression by
a transcriptomic and bio-computing approach. This was how
we selected differentially expressed genes in the brain tissue
of patients against that of control brains. Besides, we
examined alternative splicing events likely to modulate the
biological properties of genes of interest in AD. This latter
approach was developed following the observation that
such events had an impact on the biological functions of
presenilins (proteins involved in early inherited forms of AD).
Search for the molecular
determinants of neurodegenerative diseases
via transcriptomic
and candidate gene
approaches
DR2 Inserm
Group Members :
In order to successfully perform the transcriptional analysis
we first selected all chromosomal regions of interest identified
by positional cloning studies on Alzheimer’s disease. This was
how we could identify more than 463 centimorgans of the
genome distributed among 9 different chromosomes likely to
contain several candidate genes. A bio-computing analysis
made it possible to identify 2,741 genes in these regions. A
DNA chip was designed from these genes and a differential
transcriptomic analysis was made by comparing brain tissues
of AD patients with those from healthy controls. At the same
time, transcriptomic analyses were carried out on the same
tissues using Affymetrix pangenomic chips. All these findings
were thoroughly analysed with bio-computing tools in the
unit, to identify approximately 106 possible differentially
expressed candidate genes.
Richard Florence, MCU Lille 2
Ayral Anne-Marie, Engineer IPL
Grenier-Boley Benjamin, CE IPL
Demiautte Florie, Technician contrat ANR
Hansmannel Franck, Postdoctoral fellow contrat LECMA
Chouraki Vincent, PhD Student Lille 2
Laumet Geoffroy, PhD Student Lille 2
Mounier Anaïs, PhD Student Lille 2
Letronne Florent, Master 2 Student Lille 2
Key words :
Neurodegenerative disease (mild cognitive impairment,
dementia, Alzheimer s disease). Differential transcriptomics.
Differential proteomics. Bioinformatics. Biomarkers. Molecular
epidemiology. Aging. High throughout genomics. Translational
research. Prevention.
In parallel, we have also implemented a bio-computing
analysis procedure to characterise alternative splicing events
not listed in international databases. This work has led us to
make close to 6 million sequence alignments (genomic DNA
and messenger RNA). From 11,231 genes expressed in the
brain tissue showing a strong biological plausibility, we have
selected 3,572 genes likely to contain an extra, non-listed
exon. We eventually restricted the number of genes of interest
to 350 as they were located in all 463 centimorgans of
chromosomal regions of interest identified by positional
cloning studies on Alzheimer’s disease.
The objective of this theme is to identify new environmental
and genetic determinants leading to the alteration of
cognitive functions and to the conversion to dementia. This
project is focused on two aspects:
- Study of the relations between the cardiovascular risk and
dementias,
- the search for candidate genes via transcriptomic and biocomputing approaches (high throughput technologies).
Our research program in cardiovascular and neurodegenerative
diseases have enabled us to gain better insight into these two
conditions. This was how we endeavoured to assess the
relations between the intake of cholesterol-lowering agents
and the risk of developing Alzheimer’s disease. We found that a
decrease in the risk of dementia in subjects treated with lipidreducing agents (Dufouil et al, 2005) and a slower decline of
their MMSE compared to non-treated subjects (Masse et al,
2005). We have also studied several factors of genetic
susceptibility of the cardiovascular risk which may play a role in
the nervous system. This was how we excluded ACE (Bruandet
et al, in the press), APOAI (Helbecque et al, 2008) and VEGF
(Chapuis et al, 2006) genes as genetic determinants of
Alzheimer’s disease. However, we have noted that a
polymorphism of gene MMP-3 was linked to an increase in the
risk of dementia, though only in individuals who do not carry
allele 4 of the APOE gene – a major genetic determinant of
Alzheimer’s disease - (Helbecque et al, 2007). We have also
confirmed that the gene coding for paraoxonase 1 was
potentially a relevant candidate for Alzheimer’s disease
(Chapuis et al, in the press).
After these genes were selected, genetic polymorphisms
contained in these genes were systematically searched for, and
genetic epidemiologic studies were made on our case-controls
studies. Our first approach (using transcriptomic analysis)
enabled us to identify the Ornithine TransCarba-mylase
(Bensemain et al, Mol Psy, 2007), and using the second approach
(bio-computing), we identified another candidate gene, the
S100b (Lambert et al, Mol Psy 2007). In order to accelerate the
identification of new targets, we have developed a new highthroughput customised chip (Affymetrix). This was how we
could analyse 1,156 Tag-SNP’s located in 82 genes, using two
randomly selected sub-samples from 2 independent studies a French and an American one. This work enabled us to identify
a new candidate gene - NF-HEV/IL-33 located in 9p24.1.
Finally, our competences in the field of genetic epidemiology for
Alzheimer’s disease, and the availability of cases-controls studies
have enabled us to take part in the identification of new
potential determinants in cooperation with other teams. So, in
cooperation with two American teams, we were involved in the
identification of gene CALMH1, a trans-membrane glycoprotein
129
Contents
Guyant-Maréchal L, Rovelet-Lecrux A, Goumidi L, Cousin E,
Hannequin D, Raux G, Penet C, Ricard S, Macé S, Amouyel P,
Deleuze JF, Frebourg T, Brice A, Lambert JC, Campion D.
Variations in the APP promoter region and risk to Alzheimer’s disease.
Neurology, 2007, 68:632-633.
controlling concentration levels in calcium ions inside cells,
whose genetic mutation modifies both the concentration in
calcium and production of ab peptides (Dreses-Werringloer et
al, Cell, 2008).
Helbecque N, Cottel D, Hermant X, Amouyel P.
Impact of the matrix metalloproteinase MMP-3 on dementia.
Neurobiol Aging, 2007, 28:1215-1220.
Lambert JC, Ferreira S, Gussekloo J, Christiansen L, Brysbaert B,
Slagboom PE, Cottel D, Petit T, Hauw JJ, Dekosky ST, Richard F, Berr C,
Lendon CL, Kamboh IM, Mann D, Christensen K, Westendorp R, Amouyel P.
Evidence for the association of the S100beta gene with low cognitive
performance and dementia in the elderly.
Mol Psychiatry, 2007, 12:870-880.
Genetic heterogeneity of Alzheimer's disease : Complexity and advances.
Psychoneuroendocrinology, 2007, 32 (Suppl 1):S62-S70.
Leveziel N, Souied EH, Richard F, Barbu V, Zourdani A, Morineau G,
Zerbib J, Coscas G, Soubrane G, Benlian P.
PLEKHA1-LOC387715-HTRA1 polymorphisms and exudative age-related
macular degeneration in the French population.
Mol Vis, 2007, 13:2153-2159.
Considering the countless false-positives, the editors of
journals having a high impact factor significantly raised their
requirements for association studies, and before a manuscript
is accepted, we are often asked to add functionality studies or
experimental in vivo or in vitro analyses. In order to fulfil these
requirements, we work in cooperation with several teams
having expertise in the fields of cell biology such as Inserm
unit 837, in particular. We are also exploring the impact of
these factors on mild to moderate alteration of cognitive
functions in individuals without dementia. These studies
enable us to identify individuals who will eventually suffer
from a conversion to dementia. The impact of the genes so
identified is also assessed in other types of neurodegenerative diseases: fronto-temporal dementia, sporadic
Parkinson’s disease so as to determine if common
neurodegenerative processes may be identified. Finally, the
impact of candidate genes so identified is studied in
epidemiological studies defined in team 1 and team 2 on the
vascular risk (Dumont et al, Am J Hyperten, 2009).
Meirhaeghe A, Boreham CA, Murray LJ, Richard F, Davey Smith G,
Young IS, Amouyel P.
A possible role for the PPARG Pro12Ala polymorphism in preterm birth.
Diabetes, 2007, 56:494-498.
Vasseur F, Guerardel A, Barat-Houari M, Cottel D, Amouyel P,
Froguel P, Helbecque N.
Impact of a CART promoter genetic variation on plasma lipid profile in a
general population.
Mol Genet Metab, 2007, 90:199-204.
Zawadzki C, Susen S, Richard F, Haulon S, Corseaux D, Jeanpierre E,
Vincentelli A, Lucas C, Torpier G, Martin A, Van Belle E, Staels B, Jude B.
Dyslipidemia shifts the tissue factor/tissue factor pathway inhibitor
balance toward increased thrombogenicity in atherosclerotic plaques.
Evidence for a corrective effect of statins.
Atherosclerosis, 2007, 195:e117-e125.
To conclude, in the past four years, we have attained the
objectives which we had set to ourselves at the time of the
creation of the unit, particularly in terms of completion of
epidemiological studies, development of new proteomic,
transcriptomic and bio-computing screening technological
approaches and concerning the identification of determinants
for cardiovascular and neurodegenerative diseases.
Pasquier F, Richard F and Legrain S.
Maladie d’Alzheimer.
In : Traité de Santé Publique 2e édition. Eds : Médecine-Science,
Flammarion, Paris, 2007.
2008
Bruandet A, Richard F, Bombois S, Maurage CA, Masse I,
Amouyel P, Pasquier F.
Cognitive decline and survival in Alzheimer’s disease according to
education level.
Publications
2007
Bruandet A, Richard F, Tzourio C, Berr C, Dartigues JF,
Alpérovitch A, Amouyel P, Helbecque N.
Haplotypes across ACE and the risk of Alzheimer's disease : The Three-City
Study.
J Alzheimers Dis 2008, 13:333-339.
Boddaert J, Kinugawa K, Lambert JC, Boukhtouche F, Zoll J, Merval
R, Blanc-Brude O, Mann D, Berr C, Vilard J, Garabedian B,
Silvestre JS, Duyckaerts C, Amouyel P, Mariani J, Tedgui A, Mallat Z.
Evidence of a role for lactadherin in Alzheimer's disease.
Am J Pathol, 2007, 170:921-929.
Campagne F, Lambert JC, Dreses-Werringloer U, Vingtdeux V,
Lendon C, Campion D, Amouyel P, Lee AT, Gregersen PK, Davies P,
Marambaud P.
CALHM1 association with Alzheimer's disease risk response.
Cell, 2008, 135:994-996. Response.
Gutierrez-Aguilar R, Benmezroua Y, Balkau B, Marre M, Helbecque
N, Charpentier G, Polychronakos C, Sladek R, Froguel P, Neve B.
Minor contribution of Smad7 and KLF10 variants to genetic susceptibility
of type 2 diabetes.
Diabetes Metab, 2007, 33:372-378.
130
Contents
Hauw JJ, DeKosky ST, Lemoine Y, Iwatsubo T, Wavrant-De Vrièze F,
Dartigues JF, Tzourio C, Buee L, Pasquier F, Berr C, Mann D,
Lendon C, Alpérovitch A, Kamboh MI, Amouyel P, Lambert JC.
Transcriptomic and genetic studies Identify IL-33 as a candidate gene for
Mol Psychiatry, 2009, 14:1004-1016.
Chapuis J, Hannequin D, Pasquier F, Bentham P, Brice A, Leber I,
Frebourg T, Deleuze JF, Cousin E, Thaker U, Amouyel P, Mann D,
Lendon C, Campion D, Lambert JC.
Association study of the GAB2 gene with the risk of developing
Neurobiol Dis, 2008, 30:103-106.
Lambert JC, Campagne F, Marambaud P.
ALHM1, a novel gene to blame in Alzheimer disease. [Article in French].
Med Sci (Paris), 2008, 24:923-924.
Deschaintre Y, Richard F, Leys D, Pasquier F.
Treatment of vascular risk factors is associated with slower decline in
Neurology, 2009, 73:674-680.
Chapuis J, Moisan F, Mellick G, Elbaz A, Pasquier F, Hannequin D,
Lendon C, Campion D, Amouyel P, Lambert JC.
Association study of the NEDD9 gene with the risk of developing
Alzheimer's and Parkinson's disease.
Hum Mol Genet, 2008, 17:2863-2867.
Am J Hypertens, 2009, 22:993-1000.
Dreses-Werringloer U, Lambert JC, Vingtdeux V, Zhao H, Vais H,
Siebert A, Jain A, Koppel J, Rovelet-Lecrux A, Hannequin D,
Pasquier F, Galimberti D, Scarpini E, Mann D, Lendon C, Campion D,
Amouyel P, Davies P, Foskett JK, Campagne F, Marambaud P.
A polymorphism in CALHM1 influences Ca2+ homeostasis, Abeta levels,
and Alzheimer's disease risk.
Cell 2008, 133:1149-1161.
Goumidi L, Flamant F, Lendon C, Galimberti D, Pasquier F,
Scarpini E, Hannequin D, Campion D, Amouyel P, Lambert JC,
Meirhaeghe A.
An apolipoprotein A-I gene promoter polymorphism associated with
cognitive decline, but not with Alzheimer's disease.
Hansmannel F, Lendon C, Pasquier F, Dumont J, Hannequin D,
Chapuis J, Laumet G, Ayral AM, Galimberti D, Scarpini E,
Is the ornithine transcarbamylase gene a genetic determinant of
Alzheimer's disease ?
Neurosci Lett, 2009, 449:76-80.
Le Ber I, Camuzat A, Hannequin D, Pasquier F, Guedj E, RoveletLecrux A, Hahn-Barma V, van der Zee J, Clot F, Bakchine S, Puel M,
Ghanim M, Lacomblez L, Mikol J, Deramecourt V, Lejeune P,
de la Sayette V, Belliard S, Vercelletto M, Meyrignac C,
Broeckhoven CV, Lambert JC, Verpillat P, Campion D, Habert MO,
Dubois B, Brice A ; the French research network on FTD/FTD-MND.
Phenotype variability in progranulin mutation carriers: a clinical,
neuropsychological, imaging and genetic study.
Brain, 2008, 131:732-746.
An age effect on the association of common variants of ACE with
Neurosci Lett, 2009, 461:181-184.
Helbecque N, Cottel D, Amouyel P.
Low-density lipoprotein receptor-related protein 8 gene polymorphisms
and dementia.
Leveziel N, Zerbib J, Richard F, Querques G, Morineau G, FremeauxBacchi V, Coscas G, Soubrane G, Benlian P, Souied EH.
Genotype-phenotype correlations for exudative Age-related Macular
Degeneration associated with homozygous HTRA1 and CFH genotypes.
Association of plasma amyloid {beta} with risk of dementia : The
prospective Three-City Study.
Neurology, 2009, 73:847-853.
Rovelet-Lecrux A, Deramecourt V, Legallic S, Maurage CA, Le Ber I,
Brice A, Lambert JC, Frébourg T, Hannequin D, pasquier F, Campion D.
Deletion of the progranulin gene in patients with frontotemporal lobar
degeneration of Parkinson disease.
Neurobol Dis, 2008, 31:41-45.
Lambert JC, Heath S, Even G, Campion D, Sleegers K, Hiltunen M,
Combarros O, Zelenika D, Bullido MJ, Tavernier B, Letenneur L,
Bettens K, Berr C, Pasquier F, Fiévet N, Barberger-Gateau P,
Engelborghs S, De Deyn P, Mateo I, Franck A, Helisalmi S,
Porcellini E, Hanon O ; the European Alzheimer's Disease Initiative
Investigators, de Pancorbo MM, Lendon C, Dufouil C, Jaillard C,
Leveillard T, Alvarez V, Bosco P, Mancuso M, Panza F, Nacmias B,
Bossù P, Piccardi P, Annoni G, Seripa D, Galimberti D, Hannequin D,
Licastro F, Soininen H, Ritchie K, Blanché H, Dartigues JF, Tzourio C,
Gut I, Van Broeckhoven C, Alpérovitch A, Lathrop M, Amouyel P.
Nat Genet, 2009, 41:1094-1099.
2009
Bensemain F, Hot D, Ferreira S, Dumont J, Bombois J, Maurage CA,
Huot L, Hermant X, Levillain E, Hubans C, Hansmannel F, Chapuis J,
Lemoine Y, Hauw JJ, Schraen S, Lemoine Y, Buée L, Berr C, Mann D,
Pasquier F, Amouyel P, Lambert JC.
Evidence for induction of the ornithine transcarbamylase expression in
Mol Psychiatry, 2009, 14:106-116.
Bruandet A, Richard F, Bombois S, Maurage CA, Deramecourt V,
Lebert F, Amouyel P, Pasquier F.
Alzheimer's disease with cerebrovascular disease and vascular dementia :
clinical features and course compared with Alzheimer's disease.
J Neurol Neurosurg Psychiatry, 2009, 80:133-139.
Sparks DL, Hunsaker JC 3rd, Amouyel P, Malafosse A, Bellivier F,
Leboyer M, Courtet P, Helbecque N.
Angiotensin I-converting enzyme I/D polymorphism and suicidal behaviors.
Chapuis J, Boscher M, Bensemain F, Cottel D, Amouyel P, Lambert JC.
Association study of the paraoxonase 1 gene with the risk of developing
131
Contents
Laumet G, Chouraki V, Grenier Boley B, Legry V, Heath S, Zelenika D,
Epelbaum J, Berr C, Dartigues J-F, Tzourio C, Campion D, Lathrop M,
Systematic analysis of candidate genes for Alzheimer’s disease in a
French, genome-wide association study.
J Alzheimers Dis, 2010, 20:1181-1188.
Zerbib J, Seddon JM, Richard F, Reynolds R, Leveziel N, Benlian P, Borel P,
Feingold J, Munnich A, Soubrane G, Kaplan J, Rozet JM, Souied EH.
rs5888 variant of SCARB1 gene is a possible susceptibility factor for agerelated macular degeneration.
PLoS One, 2009, 4:e7341.
2010
Le Fur I, Laumet G, Richard F, Fievet N, Berr C, Rouaud O, Delcourt C,
Association study of the CFH Y402H polymorphism with Alzheimer's disease.
Goumidi L, Flamant F, Lendon C, Galimberti D, Pasquier F, Scarpini E,
Hannequin D, Campion D, Amouyel P, Lambert JC, Meirhaeghe A.
Leveziel N, Puche N, Richard F, Somner JE, Zerbib J, Bastuji-Garin S,
Cohen S, Korobelnik JF, Sahel JA, Soubrane G, Benlian P, Souied EH.
Genotypic influences on severity of exudative Age-related Macular
Degeneration.
Hansmannel F, Sillaire A, Kamboh MI, Lendon C, Pasquier F,
Hannequin D, Laumet G, Mounier A, Ayral A-M, Dekosky ST,
Hauw J-J, Berr C, Mann D, Amouyel P, Campion D, Lambert JC.
Is the urea cycle involved in Alzheimer's disease ?
J Alzheimers Dis, 2010, 21:1013-1021.
Seshadri S, Fitzpatrick AL, Ikram A, DeStefano AL, Gudnason V,
Boada M, Bis JC, Smith AV, Carassquillo MM, Lambert JC, Harold D,
Schrijvers EMC, Ramirez-Lorca R, Debette S, Longstreth WT,
Janssens CJW,Pankratz, Dartigues J-F, Hollinworth P, Aspelund T,
Hernadez I, Beiser A, Kuller LH, Koudstaal PJ, Dickson DW, Tzourio
C, Abraham R, Antunez C, Du, Y, Rotter JI, Aulchenko YS, Harris TB,
Petersen RC, Berr C, Owen MJ, Lopez-Arrieta J, Varadarajan BN,
Becker JT, Rivadeneira F, Nalls MA, Graff-Radford NR, Campion D,
Auerbach S, Rice K, Hofman A, Jonsson PV, Schmidt H, Lathrop M,
Mosley TH, Au R, Psaty BM, Uitterlinden AG, Farrer LA, Lumley T, Ruiz A,
Williams J, Amouyel P, Younkin SG, Wolf PA, Launer LJ, Lopez O, Van Duijn C,
Breteler M on behalf of the Charge, GERAD1 and EADI1 consortia.
Genome-wide association studies of alzheimer’s disease.
JAMA, 2010, 303:1864-65.
Hong MG, Alexeyenko A, Lambert JC, Amouyel P, Prince JA.
Genome-wide pathway analysis implicates intracellular transmembrane
protein transport in Alzheimer disease.
J Hum Genet, 2010, in press.
Krüger R, Sharma M, Riess O, Gasser T, Van Broeckhoven C, Theuns J,
Aasly J, Annesi G, Bentivoglio AR, Brice A, Djarmati A, Elbaz A, Farrer M,
Ferrarese C, Gibson JM, Hadjigeorgiou GM, Hattori N, Ioannidis JP,
Jasinska-Myga B, Klein C, Lambert JC, Lesage S, Lin JJ, Lynch T,
Mellick GD, de Nigris F, Opala G, Prigione A, Quattrone A, Ross OA,
Satake W, Silburn PA, Tan EK, Toda T, Tomiyama H, Wirdefeldt K,
Wszolek Z, Xiromerisiou G, Maraganore DM ; for the Genetic
Epidemiology of Parkinson's disease consortium.
A large-scale genetic association study to evaluate the contribution of
Omi/HtrA2 (PARK13) to Parkinson's disease.
Sleegers K, Lambert JC, Bertram L, Cruts M, Amouyel P,
Van Broeckhoven C.
The pursuit of susceptibility genes for Alzheimer's disease : progress and
prospects.
Trends Genet, 2010, 26:84-93.
Deciphering genetic susceptibility to frontotemporal lobar dementia.
Nat Genet, 2010, 42:189-190.
Berr C, Dartigues J-F, Tzourio C, Campion D, Lathrop M, Amouyel P.
Implication of the immune system in Alzheimer’s disease : evidence from
genome-wide pathway analysis.
J Alzheimers Dis, 2010, 20:1107-1118.
Zerbib J, Richard F, Puche N, Leveziel N, Cohen SY, Korobelnik JF,
Sahel J, Munnich A, Kaplan J, Rozet JM, Souied EH.
R102G polymorphism of the C3 gene associated with exudative agerelated macular degeneration in a French population.
Mol Vis, 2010, 16:1324-1330.
Lambert JC, Sleegers K, González-Pérez A, Ingelsson M, Beecham GW,
Hiltunen M, Combarros O, Bullido MJ, Brouwers N, Bettens K, Berr C,
Pasquier F, Richard F, Dekosky ST, Hannequin D, Haines JL, Tognoni G,
Fiévet N, Dartigues JF, Tzourio C, Engelborghs S, Arosio B, Coto E,
De Deyn P, Del Zompo M, Mateo I, Boada M, Antunez C, LopezArrieta J, Epelbaum J, Schjeide BM, Frank-Garcia A, Giedraitis V,
Helisalmi S, Porcellini E, Pilotto A, Forti P, Ferri R, Delepine M,
Zelenika D, Lathrop M, Scarpini E, Siciliano G, Solfrizzi V, Sorbi S,
Spalletta G, Ravaglia G, Valdivieso F, Vepsäläinen S, Alvarez V, Bosco P,
Mancuso M, Panza F, Nacmias B, Bossù P, Hanon O, Piccardi P,
Annoni G, Mann D, Marambaud P, Seripa D, Galimberti D, Tanzi RE,
Bertram L, Lendon C, Lannfelt L, Licastro F, Campion D, PericakVance MA, Soininen H, Van Broeckhoven C, Alpérovitch A, Ruiz A,
Kamboh MI, Amouyel P.
The CALHM1 P86L polymorphism is a genetic modifier of age at onset in
Alzheimer's Disease : a meta-analysis study.
J Alzheimers Dis, 2010, in press.
PhD
Julien CHAPUIS
Directeur de thèse Jean-Charles Lambert
« Identification de déterminants génétiques impliqués dans la composante
vasculaire de la MA, par analyses transcriptomiques, génétiques et
moléculaires
25 septembre 2008
Patent
Method for determining the risk of occurrence of Alzheimer’s disease
IPL - Inserm - CEA - Université Lille 2
25 septembre 2008
Laumet G, Petitprez V, Sillaire A, Ayral AM, Hansmannel F, Chapuis
J, Hannequin D, Pasquier F, Scarpini E, Galimberti D, Lendon C,
A study of the association between the ADAM12 and SH3PXD2A
(SH3MD1) genes and Alzheimer's disease.
Neurosci Lett, 2010, 468:1-2.
132
Contents
Genomic Analysis
Laboratory
Inserm U 744
Institut Pasteur de Lille
University Lille Nord de France
Philippe AMOUYEL
and Nathalie FIEVET-VERRECAS
Contact :
Tél. 00 33 3 20 87 71 15
Fax 00 33 3 20 87 78 94
[email protected]
Group members :
Amouyel Philippe, PU PH Lille 2
Fiévet-Verrecas Nathalie, IE IPL
Ledoux Patricia, Technician IPL
Mallet Kevin, Vacation Inserm (CDD)
Camerlynck Alisson, IPL (CDD)
Auvray Cécile, IPL (CDD)
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Contents
Technological Facilities
Nathalie FIEVET-VERRECAS, an IPL engineer, is the technical
director and is assisted by a small permanent staff of
technicians.
1) Mission
The rapid development of studies and research in the life
sciences as well as the explosion of tools for genomics and
post-genomics, beyond work in in vitro or animal models,
requires access to biological material of human origin.
For reasons essential to the protection of humans, bioethics
laws very rigorously oversee the conditions of collection,
storage and use of this human biological material. Thus any
clinical, epidemiologic or experimental study in this domain
must comply with a number of rules aimed at ensuring these
conditions are met.
3. CRB operating procedures
• Electronic control of personnel access to the site.
• Establishment of standardized procedures for quality
assurance, safety and sample traceability.
• Computerized sample management: traceability of
subjects, samples and their derivatives, biological
annotations, stock management, entries and exits, transfers
and cloning, audit of connections and data, multicriteria
research, printing barcode labels, data exportation
• Real-time control of temperatures in the various freezers : 80°C, -30°C, +4°C
• Confidentiality of information.
• Access to samples reserved exclusively to the department
that collected it.
The Genomic Analysis Laboratory, recognized as a biological
resource center (CRB) in the framework of INSERM-FRT
requests for proposals, provides teams of clinicians and
researchers with the analysis and logistic support necessary
to comply with these rules:
• homogeneity of sampling methods
• homogeneity of methods for the transformation (DNA
extraction, etc.) and processing of biological materials
• storage and preservation of samples (plasma, serum,
nucleic acids, etc.) in their initial condition, for a set or
unlimited duration, depending on the specific scientific
objectives
• information management making it possible to know at any
moment the sampling method, sample source, date, place
of storage, and all activities related to it, to ensure complete
traceability
• specific and reliable system for sample identification.
Standard procedure for management of a blood sample
The person responsible for taking the sample completes a
sample tracking document.
This anonymous form contains all information relative to the
blood sample, the treatment of the blood tubes
(centrifugation, washing…) and data related to the derived
samples obtained after treatment.
Some samples are then transferred to a laboratory where the
biochemical assays are performed; other derivatives are stored
at -80°C and constitute the biobank, while still others undergo
DNA extraction.
To enable the exchange of biological resources and the data
related to them between different centers, INSERM and the
Ministry of Research established quality assurance procedures
for CRBs in 2006. National quality assurance standards for CRBs
are now being drafted under the aegis of AFNOR.
This step is an essential prerequisite for the emergence of a
national network of biobanks.
All data from the sample tracking document are then fully
entered into the database with Databiotec sample
management software (entry of sample source, derived
products, characterization, number…)
2. Resources
4. Projects underway
2.1. Premises and equipment
The Genomic Analysis Laboratory occupies an area of 135 m2
and has a 37m2 air-conditioned room for –80°C freezers.
Its equipment includes a Microbiological Safety Cabinet, the
material and supplies necessary for work in molecular biology,
and the infrastructure necessary for sample storage, that is, 13
-80°C freezers and a system of computerized sample
management.
2.2. Personnel
The Genomic Analysis Laboratory is supervised by Philippe
AMOUYEL, University professor and hospital physician at the
University of Lille 2, Director of the UMR 744 Unit “Public
Health and Molecular Epidemiology of aging related diseases”
, Director of the Institut Pasteur de Lille and Director of the
Scientific Cooperation Foundation for Alzheimer’s disease and
related disorders
The LAG-CRB of the Institute Pasteur of Lille manage 9 national
and international collections.
The Three Cities (3-C) Study : Bordeaux, Dijon and
Montpellier.
Launched with the support of the Foundation for Medical
Research in 1997, its objective is "to estimate the risk of
dementia and severe degeneration attributable to risk factors
and to vascular disease."
The cohort includes 9692 persons older than 65 years,
followed for 4 years. Each participant undergoes a battery of
tests : questionnaire, cognitive tests, blood sample,
electrocardiogram and carotid ultrasound.
8860 subjects agreed to give blood samples ; these samples
generated 221 500 derived samples (plasma, red blood cells,
and serum), 180 550 of which are stored at LAG.
3 500 subjects had an MRI (magnetic resonance imaging).
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These images will be analyzed by automatic software that can
detect cerebral lesions and calculate tissue volume, in
particular, of gray matter.
In the long run, the 3C study should provide answers to two
essential questions : who are the people at highest risk for
whom preventive action is possible ? And to what extent does
this prevention favorably modify the disease course ?
adolescence and the development of nontransmissible diseases.
LAG extracted DNA samples for 1 143 subjects.
Cadisp : Cervical Artery Dissections and Ischemic Stroke
Patients - for France : Amiens - Dijon - Besançon - Paris (x2)
- Lille
This study, initiated in 2004, is a European Consortium
performing research on ischemic stroke in the young and in
particular on cervical artery dissection (the most common
cause of ischemic stroke stroke in young people).
The CADISP-genetic study (2006-2008) is one among other
collaborative research projects of the CADISP Consortium with
the following goals :
• Look for genetic variants associated with CAD
• Look for environmental risk factors of CAD
• Address therapeutic aspects in the setting of a multicenter
registry
LAG extracted DNA samples for 549 subjects.
Covadis : Cognitive vascular diseases - Dijon
Continuation of the 3-C Study in Dijon, this new study will make
available a larger number of vascular events and cases of
dementia by extending follow-up for 4 years in a subcohort of
subjects who had an MRI as part of the 3C study (1606 subjects
and 35 015 samples of plasma and serum) stored at LAG.
Paradigme : Parkinson and Alzheimer diseases: impact of
gene, metabolism and environment - Lille CHRU
Conducted as part of an INSERM 2002 funding program
(collection of human biological material for research
purposes), the aim of this study is to identify new factors of
genetic susceptibility involved principally in Alzheimer and
Parkinson diseases, both neurodegenerative, as well as their
potential interactions with environmental factors.
796 subjects with disease were seen between May 2003 and
January 2006. Blood samples made it possible to collect a
biobank of 18 490 derived samples (plasma, red blood cells,
and serum) stored at LAG.
Young Heart Study : Northern Ireland
Northern Ireland is one of the countries with the highest rates
of coronary disease in the world (from the age of 15 years, 1
Irish child in 4 is at risk of a heart attack). The aim of this study
is to discover the risk factors leading to the development of
these diseases in adulthood.
This study, funded by the Northern Ireland Fund, the Heart
and Stroke Association, the British Heart Foundation and the
Wellcome Trust, began in 1988.
The cohort includes 509 children aged 12 years and 506
children aged 15 years at inclusion. These children were
reexamined in the same conditions (same physical tests) in
1992 and then in 1997.
LAG extracted DNA for 444 subjects.
Euroaspire III : European Activity on Secondary and Primary
Prevention in order to Reduce Events 22 countries : Italy, France,
Belgium, Greece, the Netherlands, Slovenia, Romania, Bulgaria ,
Ireland, Lithuania, Latvia, Germany, Finland, Cyprus, Hungary,
Poland, Croatia, Spain, Czech Republic, Turkey and England.
The aim of this multicenter European study is to identify risk
factors in patients with coronary diseases.
The Lille team selected 342 subjects hospitalized for coronary
diseases. LAG is storing the 3382 French samples (plasma, sera,
white blood cell).
SU.VI.MAX : Antioxidant Vitamin and Mineral
Supplementation. France
Launched in October 1994, by the Conservatoire National des
Arts et Métiers, INSERM, the Ministries of Health, Agriculture and
Research, and the city of Paris, this study has 2 objectives :
• assess the efficacy of antioxidant vitamin and mineral
supplementation in the prevention of cardiovascular
diseases and cancer,
• construct a database of the food intake of the French
population.
Monalisa and MonalisaNut : Monitoring National Arterial
Risk - Lille, Strasbourg and Toulouse
This survey, which began in October 2005, is intended to
estimate the prevalence of cardiovascular risk factors
(hypertension, dyslipidemia, diabetes, overweight, obesity,
sedentary lifestyle, and smoking) in the population aged 3574 years in the regions of Lille, Strasbourg and Toulouse (1600
subjects randomly selected in each geographic zone).
LAG stores the samples from all 3 centers, that is to say 58 173
samples (plasma, sera) derived from the blood samples of 4
797 subjects.
LAG extracted DNA from Lille and Strasbourg samples for 3
168 subjects.
Between 1994 and 2002, 13 017 volunteers (7886 women
aged 35-60 years and 5141 men aged 45-60 years)
participated in this study.
The volunteers were allocated to one of two groups: one
received the SUVIMAX pill, and the other a placebo capsule
with no active substance, daily for 8 years. The SUVIMAX
cocktail included antioxidant nutritional supplements
composed of : Beta-carotene 6 mg, Vitamin C 120 mg, Vitamin
E 30 mg, selenium 100 µg, and zinc 20 mg.
Helena : Healthy Lifestyle in Europe by Nutrition in
Adolescence
11 countries : Greece, England, Germany, Belgium, Crete,
France, Hungary, Italy, Sweden, Austria and Spain
This study will make it possible to obtain valid and reliable
information on the nutritional status of European adolescents
(dietary habits, nutrition knowledge and eating attitudes, food
choices and preferences, metabolic profile, body composition,
vitamin status, physical activity, genetic variations, etc.) to
improve our understanding of the relations between
After eight years of follow-up (questionnaires, health
examinations, dietary surveys, plasma assays, and specific
tests in the case of diseases), the results show that this intake
of antioxidant vitamins and minerals reduced by 31% cancer
incidence and overall mortality in men. This reduction affected
most cancer sites: gastrointestinal, ORL, respiratory, cutaneous
LAG extracted DNA from samples for 955 subjects, collected
in 1994 and 1995.
221
Contents
Publications
2008
Le Fur I, Laumet G, Richard F, Fievet N, Berr C, Rouaud O,
Delcourt C, Amouyel P, Lambert JC.
Association study of the CFH Y402H polymorphism with Alzheimer's
disease.
Neurobiol Aging, 2008, apr 21.
2009
Association of plasma amyloid beta with risk of dementia: the prospective
Three-City Study.
Neurology, 2009, 73:847-853.
Lambert JC, Health S, Even, Campion D, Sleegers K, Hiltunen M,
Combarros, Zelenika D, Bullido MJ, Tavernier B, Lentenneur L,
Bettens K, Berr C, Pasquier F, Fievet N, et al.
Nat Genet, 2009, 41:1047-1048.
Hauw JJ, et al.
Transcriptomic and genetic studies identify IL-33 as a candidate gene for
Mol Psychiatry, 2009 Feb 10 [Epub ahead of print].
2010
Berr C, Dartigues JF, Tzourio C, Campion D, Lathrop M, Amouyel P.
Implication of the Immune System in Alzheimer's Disease : Evidence from
Genome-Wide Pathway Analysis.
J Alzheimers Dis, 2010, Apr 22.
Laumet G, Chouraki V, Boley BG, Legry V, Heath S, Zelenika D,
Epelbaum J, Berri C, Dartigues JF, Tzourio C, Campion D, Lathrop M,
Systematic Analysis of Candidate Genes for Alzheimer's Disease in a
French, Genome-Wide Association Study.
J Alzheimers Dis, 2010, Apr 22.
222
Contents

2009 - Institut Pasteur de Lille

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