Homozygosity for the Ala allele of the PPARγ2 Pro12Ala polymorphism is associated with reduced risk of coronary artery disease.

Several studies suggest that the peroxisome proliferator-activated receptor gamma (PPAR gamma) is involved in atherogenesis. The Pro12Ala polymorphism in the gene encoding PPAR gamma (PPAR gamma 2gene) influences the risk for type 2 diabetes. Two population-based studies have shown that the Ala allele is associated with reduced carotid intimal-medial thickness (IMT). However, studies focusing on acute clinical events have yielded conflicting results. Our aim was to evaluate the role of the Pro12Ala PPAR gamma 2 polymorphism on the risk of coronary artery disease (CAD) in an Italian population with a case-controlled genetic association study in which 478 CAD patients and 218 controls were genotyped for the Pro12Ala polymorphism. CAD was diagnosed by angiography. We found that homozygotes for the Ala12 allele had a significantly reduced risk of CAD after adjusting for diabetes, sex, age, body mass index (BMI), smoking, lipids and hypertension (OR = 0.007; 95% C. I. = 0.00-0.32 p < 0.011). In this case-control study, homozygosity for the Ala allele at codon 12 of the PPAR gamma 2 gene resulted in reduced risk of CAD. This is consistent with reports from previous studies focusing on atherosclerosis and myocardial infarction.