Deletion Polymorphism of the Angiotensin I-Converting Enzyme Gene Is Associated with Increased Plasma Angiotensin-Converting Enzyme Activity but Not with Increased Risk for Myocardial Infarction and Coronary Artery Disease

Abstract

Previous research has shown that the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene is a major determinant of plasma ACE activity. It has been suggested that persons with the DD genotype (those who express, on average, the highest levels of circulating ACE) have an increased risk for myocardial infarction and coronary artery disease, particularly if they are otherwise at low risk. Subsequent studies, however, have not confirmed that ACE I/D gene polymorphism is a risk factor for coronary artery disease and myocardial infarction. To investigate the association between the I/D polymorphism of the ACE gene and the risk for coronary artery disease and myocardial infarction in patients in whom coronary artery disease status was documented by angiography. Cross-sectional study. University medical center. 209 male case-patients with coronary artery disease and 92 male controls without coronary artery disease, as documented by coronary angiography. Assessment of the cardiac risk profile by questionnaire; classification of patients by the degree of coronary artery stenosis; levels of lipoproteins, apolipoproteins, and fibrinogen; and ACE I/D gene polymorphism assessed by polymerase chain reaction amplification. Plasma ACE activity was significantly associated with ACE I/D gene polymorphism. The ACE genotype was not associated with the presence of coronary artery disease or myocardial infarction. If a recessive effect of the D allele was assumed (DD compared with DI and II), the relative risk was 1.00 (95% CI, 0.76 to 1.30) for coronary artery disease and 1.03 (CI, 0.77 to 1.38) for myocardial infarction. Results of analyses were also negative when a dominant effect of the D allele was assumed and when low-risk subgroups were examined. The established risk factors age and apolipoprotein B level emerged as the most important risk predictors in multivariate analyses, followed by diastolic blood pressure and fasting glucose levels. In an angiographically defined study sample, ACE I/D gene polymorphism was not associated with an increased risk for coronary artery disease or myocardial infarction, despite its effects on plasma ACE activity.