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- peroxisome proliferator activated receptor alpha
- genetic polymorphisms
- myocardial infarction
Peroxisome proliferator activated receptor alpha (PPARα), 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.1–3 This nuclear receptor is the cellular target of the fibrate drugs, which can lower triglyceride levels and reduce risk of acute coronary ischaemic events.4,5 Gender specific differences in PPARα expression and in response to PPARα deficiency have been observed in many animal studies.6–12
There is emerging evidence suggesting that, in humans, variation in the gene encoding PPARα contributes to interindividual variability in lipid levels,13,14 body weight,15,16 and risk of coronary ischaemic events.17 In this study, we examined the PPARα gene Leu162Val and intron 7 G>C polymorphisms17–19 in a large cohort of Caucasian patients with coronary artery disease, and found that the genotypic effects of PPARα on plasma triglyceride level, hypertension prevalence, and myocardial infarction differed between men and women.
SUBJECTS AND METHODS
The subjects in this study were participants in the Southampton atherosclerosis study, all having atherosclerosis in at least one coronary artery, as described previously.20,21 The demographic and clinical characteristics of the subjects are summarised in table 1. Data on fasting levels of triglycerides, total cholesterol, and HDL cholesterol were available for 1017, 1110, and 630 subjects, respectively, measured in the clinical chemistry department of the Southampton General Hospital using standard quality controlled enzymatic methods. A total of 649 patients were receiving statin treatment and 16 were receiving fibrate (PPARα agonist) treatment. The study was approved by the local research ethics committee, and all subjects gave written consent. A 10 ml blood sample was taken from each participant, and DNA was extracted using a salt precipitation method.
Determination of genotypes
Genotypes for the Leu162Val and …
This work was supported by the British Heart Foundation (PG98/183, PG98/192, PG2001/105, PG02/053).