ACE gene polymorphism: Ischemic heart disease and longevity in 10150 individuals - A case-referent and retrospective cohort study based on the Copenhagen City Heart Study

Background Homozygosity for the deletion allele (D) of the angiotensin-converting enzyme (ACE) gene insertion-deletion polymorphism has been suggested to be a potent risk factor for myocardial infarction. With one exception, the samples studied so far have been small and/or ethnically heterogeneous, and most investigators have studied men only. Methods and Results We investigated the association between ACE genotype and myocardial infarction as well as other manifestations of ischemic heart disease for both women and men in a case-referent study (n=10 150) as well as in a retrospective cohort study (n=7263). The cohort was from the ethnically homogeneous Danish population. Case subjects were from the same geographic area and had ischemic heart disease. Irrespective of the assumed degree of relative penetrance of the D allele, the odds ratios were not significantly different from 1.0 (P>.05) for ischemic heart disease, severe stenosis on coronary angiography, or myocardial infarction. There was also no association between ACE genotype and phenotypic variation in recognized risk factors for ischemic heart disease. Finally, the relative frequency of the D allele did not change as a function of age in subjects aged from 20 to greater than or equal to 80 years. Conclusions In two large studies, a case-referent study and a retrospective cohort study in an ethnically homogeneous white population, there was no evidence for a statistically significant difference in the development of myocardial infarction or any other manifestations of ischemic heart disease between genotype classes of the ACE gene polymorphism in either women or men.