Glutathione S-transferase M1 null genotype is associated with a decreased risk of myocardial infarction

Tobacco smoke is a major cause of both cancer and vascular disease. Althoug h its carcinogenic role via induction of DNA damage and mutation is well es tablished, the mechanisms involved in vascular disease remain unclear. One possibility is that DNA damage causes smooth muscle cell proliferation in t he intima of arteries, thereby contributing to atherothrombotic processes. The binding of chemicals to DNA is modulated by detoxification enzymes, inc luding glutathione S-transferases (GST) and microsomal epoxide hydrolase (E PXH). We therefore examined whether polymorphisms in these genes influence risk of cardiovascular disease. Blood was obtained from 398 patients admitt ed for angiographic investigation of chest pain and 196 age- and sex-matche d controls. Patients were subdivided into those with and without previous a cute myocardial infarction (AMI). DNA was analyzed for deletions in the GST M1 and T1 genes and for substitutions in EPXH and GSTP1 genes. The GSTM1 nu ll genotype occurred at a significantly lower frequency in the AMI patient group (48%) compared both to patients with no history of AMI (59%) and to t he control group (57.2%). When subjects were stratified for smoking status, a significant association was observed only in smokers, suggesting the pol ymorphism is more important in the presence of tobacco smoke exposure. The association remained significant after adjusting for age, sex, and stenosis (presence or absence). No significant associations were observed between t he other genotypes and cardiovascular disease (X-2 test; P>0.1). The result s of this study indicate that the GSTM1 null genotype is protective against AMI, an effect that is more marked in smokers. However, further study is r equired in order to elucidate the as yet unexplained, mechanisms underlying this association.