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

BACKGROUND

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.

METHODS AND RESULTS

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).

CONCLUSION

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.