ANGIOTENSIN-CONVERTING ENZYME GENOTYPES AND RISK FOR MYOCARDIAL-INFARCTION IN WOMEN

Objectives. We tested for an association between the angiotensin-conve rting enzyme (ACE) DD polymorphic genotype and myocardial infarction ( MI) in a sample group composed exclusively of women. Background. The h uman ACE gene occurs with either an insertion (I allele) or a deletion (D allele) of a 287-base pair (bp) Alu element. Part of the variance in serum ACE levels may be accounted for by this polymorphism. Also, t he DD genotype has been associated with an increased risk of MI in pre dominantly male populations. However, the risk in women is poorly defi ned. Methods. Genomic DNA was extracted from buffy coat blood using a phenol/chloroform method. Angiotensin converting enzyme alleles were i dentified using primers to bracket the insertion region in intron 16. Amplification using polymerase chain reaction allowed identification o f a 490-bp (I allele) or a 190-bp (D allele) product, or both. Results . Allelic and genotypic frequencies in control subjects were similar t o those reported in mostly male populations, and frequencies of genoty pes were in the Hardy-Weinberg equilibrium. In contrast, the distribut ion of genotypes in patients with MI diverged from the equilibrium, Sp ecifically, DD genotypic frequency was increased in women with (n = 14 1) versus without (n = 338) a previous MI (39% vs. 29%, odds ratio [OR ] 1.54, 95% confidence interval 1.02 to 2.32, p < 0.04). Risk was part icularly increased in women <60 years old (OR 2.04, p < 0.05). In cont rast, the DD genotype did not predict angiographic coronary artery dis ease. Conclusions. Consistent with findings in male-dominated populati ons, a modest association of the ACE DD genotype with MI was found in women. The basis for this association requires further study. (C) 1998 by the American College of Cardiology.