Joint effects of an aldosterone synthase (CYP11B2) gene polymorphism and classic risk factors on risk of myocardial infarction

Background-The -344C allele of a 2-allele (C or T) polymorphism in the prom oter of the gene encoding aldosterone synthase (CYP11B2) is associated with increased left ventricular size and mass and with decreased baroreflex sen sitivity, known risk factors for morbidity and mortality associated with my ocardial infarction (MI), We hypothesized that this polymorphism was a risk factor for MI. Methods and Results-We used a nested case-control design to investigate the relationships between this polymorphism and the risk of nonfatal MI in 141 cases and 270 matched controls from the Helsinki Heart Study, a coronary p rimary prevention trial in dyslipidemic, middle-aged men. There was a nonsi gnificant trend of increasing risk of MI with number of copies of the -334C allele. However, this allele was associated in a gene dosage-dependent man ner with markedly increased MI risk conferred by classic risk factors. Wher eas smoking conferred a relative risk of MI of 2.50 (P=0.0001) compared wit h nonsmokers in the entire study population, the relative risk increased to 4.67 in -344CC homozygous smokers (relative to nonsmokers with the same ge notype, P=0.003) and decreased to 1.09 in -344TT homozygotes relative to no nsmokers with this genotype, Similar joint effects were noted with genotype and decreased HDL cholesterol level as combined risk factors. Conclusions-Smoking and dyslipidemia are more potent risk factors for nonfa tal MI in males who have the -344C allele of CYP11B2.