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

Background: Peroxisome proliferator-activated receptor gamma (PPAR gamma) a s a transcription factor plays an important role in lipid metabolism, gluco se homeostasis, insulin sensitivity, obesity, diabetes, foam cell formation and atherogenesis. Methods and Results: We have studied distribution of th e PPAR gamma C161-->T substitution at exon 6 in 647 Australian Caucasian pa tients aged less than or equal to 65 years (484 men and 163 women) recruite d consecutively, with or without angiographically documented coronary arter y 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-Wein berg equilibrium and not different between men and women. The BMI and waist to hip ratio (WHR) among patients with CC, <(CT+TT)under bar> genotypes we re not different (P=0.878, P=0.677). However there was a significant associ ation 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 e vident 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 ass ociated with a reduced CAD risk, particularly among CT heterozygous patient s, but not with obesity in Australian Caucasian patients. It implicates tha t 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. (C) 1999 Elsevier Science B.V. All rights reserved.