Analysis of promoter region polymorphism in the aldosterone synthase gene (CYP11B2) as a risk factor for myocardial infarction.
Several polymorphisms in genes of the reninangiotensin-aldosterone system have been found to have pleiotropic effects on cardiovascular disorders. Recently, a polymorphism (-344 C/T) in the promoter region of the aldosterone synthase gene (CYP11B2), which may influence plasma aldosterone levels, has been reported to strongly influence left ventricular diameters and mass in young adults and arterial stiffness in essential hypertensives. We investigated any association with risk of myocardial infarction (MI). CYP11B2 -344 polymorphism genotypes were determined by polymerase chain reaction (PCR) in 542 acute MI cases and 500 control subjects without history of coronary disease. All subjects were white and <75 years old. There was no significant difference in either genotype distributions (cases CC 17%, CT 52%, TT 31%; controls CC 22%, CT 47%, TT 31%, P = .10) or allele frequencies (cases C/T 0.43/0.57, controls C/T 0.46/0.54, P = .39) between cases and controls. The odds ratio (OR) for MI associated with the CC genotype was 0.75 (0.54-1.05), and remained insignificant when analysis was restricted to the 129 (24%) cases and 193 (37%) controls < 55 years of age (OR 0.68 [0.36-1.27], P = .20). In further analyses, there was no interaction of the polymorphism with other cardiovascular risk factors (smoking, hypertension, diabetes, body mass index, or cholesterol level) in determining MI risk, and the polymorphism did not influence the frequency of these risk factors in either cases or controls. In the case cohort, age at MI was not significantly different in subjects with the three genotypes (CC 61.2 +/- 9.8 years, CT 61.8 +/- 9.1 years, TT 62.2 +/- 9.0 years, P = .69). We conclude that the aldosterone synthase -344 promoter region polymorphism does not significantly influence the risk of MI either directly or via interaction with other risk factors.