Association between the ACE genotype and coronary artery disease. Insights from studies on restenosis, vasomotion and thrombosis

Abstract

Circulating levels of angiotensin-converting enzyme (ACE) in humans are linked with an insertion (I)/deletion (D) polymorphism in the ACE gene: DD genotype bearers have higher levels of ACE than either ID or II genotype bearers. Recent studies have suggested that the ACE DD genotype may be associated with a higher risk of coronary artery disease. The aim of this paper is to review studies on the influence of I/D polymorphism on coronary restenosis, coronary vasomotion and coronary thrombosis. The renin angiotensin system has been implicated in the pathogenesis of neointimal hyperplasia in experimental models. In humans, I/D polymorphism is not associated with restenosis after balloon angioplasty but is strongly associated with restenosis after coronary stent implantation. This may be explained by the fact that the contribution of neointimal hyperplasia to restenosis is much more important after coronary stent implantation than after balloon angioplasty. The renin angiotensin system may participate in the regulation of coronary vasomotion. An association between I/D polymorphism and coronary artery spasm has been reported. An increased production of plasminogen activator inhibitor-I and an increase in platelet aggregability may explain the higher risk of coronary thrombosis in subjects with high levels of ACE. The ACE I/D genotype has been associated with a lower incidence of a patent infarct-related artery after myocardial infarction and with a higher risk of total occlusion of the dilated site 6 months after successful balloon angioplasty. These studies suggest that the influence of the I/D polymorphism on coronary artery disease may be multifactorial. Possible mechanisms include interactions with neointimal formation, coronary artery spasm and coronary thrombosis.