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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2403.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Cardiovascular Risk in Type 2 Diabetes Is Associated With Variation at the PPARG Locus

A Go-DARTS Study

Alex S.F. Doney; Bettina Fischer; Graham Leese; Andrew D. Morris; Colin N.A. Palmer

From the Institute for Cardiovascular Research (B.F., C.N.A.P.), Biomedical Research Centre, and the Department of Medicine and Therapeutics (A.S.F.D., G.L., A.D.M.), Ninewells Hospital and Medical School, Dundee, Scotland.

Correspondence to Dr Colin N.A. Palmer, Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, DD1 9SY. E-mail nuclear-receptor{at}dundee.ac.uk

Objective— The Pro12Ala polymorphism of PPARG modulates risk of developing type 2 diabetes. The Ala allele has also been associated with a reduced risk of cardiovascular events. We have shown previously that the linked T allele of the C1431T polymorphism influences Ala12-associated diabetes risk and that the 2 polymorphisms have opposing associations with body weight. We therefore investigated the association of these 2 variants with cardiovascular events in people with type 2 diabetes.

Methods and Results— We performed a cohort study of 2016 individuals and used Cox proportional hazards to analyze risk of myocardial infarction or death by PPARG Pro12Ala and C1431T genotypes, adjusting for age, sex, and smoking status. In individuals enrolled <70 years of age, the hazard for a first nonfatal event associated with the Ala12 allele was 0.21 (CI, 0.06 to 0.69; P=0.01) and the T1431 allele 9.9 (CI, 1.90 to 51.29; P=0.007). These opposing associations remained significant after correction for other conventional risk factors. The T1431 allele was also associated with all-cause mortality.

Conclusions— This study confirms the association of the Ala12 allele with reduced risk of myocardial infarction in a type 2 diabetic population and demonstrates that the T allele independently associates with an increased risk.

Variants of PPARG may influence cardiovascular risk. The association of the linked Pro12Ala and C1431T variants with myocardial infarction was investigated in a large cohort of patients with type 2 diabetes. Ala12 was associated with a significantly decreased risk and T1431 a significantly increased risk.

Key Words: type 2 diabetes • myocardial infarction • PPARG • polymorphism

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