Peroxisome Proliferator-Activated Receptor Gamma Polymorphisms and Coronary Heart Disease
Jean Dallongeville,
Carlos Iribarren,
Jean Ferrières,
Liisa Lyon,
Alun Evans,
Alan S. Go,
Dominique Arveiler,
Stephen P. Fortmann,
Pierre Ducimetière,
Mark A. Hlatky,
Philippe Amouyel,
Audrey Southwick,
Thomas Quertermous,
Aline Meirhaeghe
Affiliations
Jean Dallongeville
Service d'Epidémiologie et de Santé Publique, Institut Pasteur de Lille, Lille; INSERM, U744, Lille; Université Nord de France, Lille; UDSL, 59019 Lille, France
Carlos Iribarren
Kaiser Permanente Division of Research, Oakland, CA 94612, USA
Jean Ferrières
INSERM, U558, Toulouse, Department of Epidemiology, Paul Sabatier-Toulouse Purpan University, 31073 Toulouse, France
Liisa Lyon
Kaiser Permanente Division of Research, Oakland, CA 94612, USA
Alun Evans
The Department of Epidemiology and Public Health, Queen’s University Belfast, Belfast BT71NN, Northern Ireland, UK
Alan S. Go
Kaiser Permanente Division of Research, Oakland, CA 94612, USA
Dominique Arveiler
Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Faculty of Medicine, 67085 Strasbourg, France
Stephen P. Fortmann
Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA 94305-5705, USA
Pierre Ducimetière
INSERM, U780, 94807 Villejuif, Hôpital Kremlin-Bicêtre, France
Mark A. Hlatky
Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA
Philippe Amouyel
Service d'Epidémiologie et de Santé Publique, Institut Pasteur de Lille, Lille; INSERM, U744, Lille; Université Nord de France, Lille; UDSL, 59019 Lille, France
Audrey Southwick
Stanford Human Genome Center, Stanford, CA 94304, USA
Thomas Quertermous
Falk Cardiovascular Research Center, Stanford Falk Cardiovascular Research Building, Stanford, CA 94305-5406, USA
Aline Meirhaeghe
Service d'Epidémiologie et de Santé Publique, Institut Pasteur de Lille, Lille; INSERM, U744, Lille; Université Nord de France, Lille; UDSL, 59019 Lille, France
Single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor γ (PPARG) gene have been associated with cardiovascular risk factors, particularly obesity and diabetes. We assessed the relationship between 4 PPARG SNPs (C-681G, C-689T, Pro12Ala, and C1431T) and coronary heart disease (CHD) in the PRIME (249 cases/494 controls, only men) and ADVANCE (1,076 cases/805 controls, men or women) studies. In PRIME, homozygote individuals for the minor allele of the PPARG C-689T, Pro12Ala, and C1431T SNPs tended to have a higher risk of CHD than homozygote individuals for the frequent allele (adjusted OR [95% CI] = 3.43 [0.96–12.27], P=.058, 3.41 [0.95–12.22], P=.060 and 5.10 [0.99–26.37], P=.050, resp.). No such association could be detected in ADVANCE. Haplotype distributions were similar in cases and control in both studies. A meta-analysis on the Pro12Ala SNP, based on our data and 11 other published association studies (6,898 CHD cases/11,287 controls), revealed that there was no evidence for a significant association under the dominant model (OR=0.99 [0.92–1.07], P=.82). However, there was a borderline association under the recessive model (OR=1.29 [0.99–1.67], P=.06) that became significant when considering men only (OR=1.73 [1.20–2.48], P=.003). In conclusion, the PPARG Ala12Ala genotype might be associated with a higher CHD risk in men but further confirmation studies are needed.
