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

MICHAEL H. WILSON^*, PETER J. GRANT, LAURA J. HARDIE^* and CHRISTOPHER PAUL WILD^*1

^* Molecular Epidemiology Unit and
Molecular Vascular Medicine Unit, School of Medicine, University of Leeds, LS2 9JT, U.K.

¹Correspondence: Molecular Epidemiology Unit, Algernon Firth Building, School of Medicine, University of Leeds, LS2 9JT, U.K. E-Mail: c.p.wild{at}leeds.ac.uk

Tobacco smoke is a major cause of both cancer and vascular disease. Although its carcinogenic role via induction of DNA damage and mutation is well established, the mechanisms involved in vascular disease remain unclear. One possibility is that DNA damage causes smooth muscle cell proliferation in the intima of arteries, thereby contributing to atherothrombotic processes. The binding of chemicals to DNA is modulated by detoxification enzymes, including glutathione S-transferases (GST) and microsomal epoxide hydrolase (EPXH). We therefore examined whether polymorphisms in these genes influence risk of cardiovascular disease. Blood was obtained from 398 patients admitted for angiographic investigation of chest pain and 196 age- and sex-matched controls. Patients were subdivided into those with and without previous acute myocardial infarction (AMI). DNA was analyzed for deletions in the GSTM1 and T1 genes and for substitutions in EPXH and GSTP1 genes. The GSTM1 null 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 the control group (57.2%). When subjects were stratified for smoking status, a significant association was observed only in smokers, suggesting the polymorphism 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 the other genotypes and cardiovascular disease (X² test; P>0.1). The results 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 required in order to elucidate the as yet unexplained, mechanisms underlying this association.—Wilson, M. H., Grant, P. J., Hardie, L. J., Wild, C. P. Glutathione S-transferase M1 null genotype is associated with a decreased risk of myocardial infarction.

Key Words: Key Word: epoxide hydrolase • acute myocardial infarction • GSTM1 • RFLP • case-control study

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