A PROSPECTIVE EVALUATION OF AN ANGIOTENSIN-CONVERTING-ENZYME GENE POLYMORPHISM AND THE RISK OF ISCHEMIC-HEART-DISEASE

Background. In a previous study, men with a history of myocardial infa rction were found to have an increased prevalence of homozygosity for the deletional allele (D) of the angiotensin-converting-enzyme (ACE) g ene, The D allele is associated with higher levels of ACE, which may p redispose a person to ischemic heart disease. We investigated the asso ciation between the ACE genotype and the incidence of myocardial infar ction, as well as other manifestations of ischemic heart disease, in a large, prospective cohort of U.S. male physicians, Methods. In the Ph ysicians' Health Study, ischemic heart disease as defined by angina, c oronary revascularization, or myocardial infarction developed in 1250 men by 1992, They were matched with 2340 controls according to age and smoking history. Zygosity for the deletion-insertion (D-I) polymorphi sm of the ACE gene was determined by an assay based on the polymerase chain reaction, Data were analyzed for both matched pairs and unmatche d samples, with adjustment for the effects of known or suspected risk factors by conditional and non-conditional logistic regression, respec tively. Results. The ACE genotype was not associated with the occurren ce of either ischemic heart disease or myocardial infarction, The adju sted relative risk associated with the D allele was 1.07 (95 percent c onfidence interval, 0.96 to 1.19; P = 0.24) for ischemic heart disease and 1.05 (95 percent confidence interval, 0.89 to 1.25; P = 0.56) for myocardial infarction, if an additive mode of inheritance is assumed, Additional analyses assuming dominant and recessive effects of the D allele also failed to show any association, as did the examination of low-risk subgroups, Conclusions. In a large, prospectively followed po pulation of U.S. male physicians, the presence of the D allele of the ACE gene conferred no appreciable increase in the risk of ischemic hea rt disease or myocardial infarction.