Evidence of differing genotypic effects of PPARalpha in women and men.

P eroxisome proliferator activated receptor alpha (PPARa), a ligand inducible transcription factor of the nuclear receptor family, plays an important part in the regulation of many genes involved in lipid metabolism and atherogenesis. This nuclear receptor is the cellular target of the fibrate drugs, which can lower triglyceride levels and reduce risk of acute coronary ischaemic events. 5 Gender specific differences in PPARa expression and in response to PPARa deficiency have been observed in many animal studies. There is emerging evidence suggesting that, in humans, variation in the gene encoding PPARa contributes to interindividual variability in lipid levels, 14 body weight, 16 and risk of coronary ischaemic events. In this study, we examined the PPARa gene Leu162Val and intron 7 G.C polymorphisms in a large cohort of Caucasian patients with coronary artery disease, and found that the genotypic effects of PPARa on plasma triglyceride level, hypertension prevalence, and myocardial infarction differed between men and women.