Peroxisome proliferator-activated receptor gamma C161-->T polymorphism and coronary artery disease

Peroxisome proliferator-activated receptor gamma (PPAR gamma) as a transcription factor plays an important role in lipid metabolism, glucose homeostasis, insulin sensitivity, obesity, diabetes, foam cell formation and atherogenesis.

We have studied distribution of the PPAR gamma C161-->T substitution at exon 6 in 647 Australian Caucasian patients aged < or = 65 years (484 men and 163 women) recruited consecutively, with or without angiographically documented coronary artery disease (CAD). The frequencies of the CC, CT and TT genotypes were 69.8%, 27.7% and 2.5% and the 'T' allele frequency 0.163. They were in Hardy-Weinberg equilibrium and not different between men and women. The BMI and waist to hip ratio (WHR) among patients with CC, CT + TT genotypes were not different (P = 0.878, P = 0.677). However there was a significant association between the polymorphism and CAD. The 'T' allele carriers (CT + TT) had significantly reduced CAD risk compared to the CC homozygotes (odds ratio: 0.457, 95% CI: 0.273-0.763, P = 0.0045) in a logistic regression model after controlling other known risk factors. This reduced risk was particularly evident among CT heterozygotes (odds ratio: 0.466, 95% CI: 0.291-0.746, P = 0.0015), who also had lower apo B and total cholesterol to HDL-C ratios (P < 0.05).

We report that the PPAR gamma C161-->T substitution is associated with a reduced CAD risk, particularly among CT heterozygous patients, but not with obesity in Australian Caucasian patients. It implicates that the PPAR gamma may have a significant role in atherogenesis, independent of obesity and of lipid abnormalities, possibly via a direct local vascular wall effect.