The D allele of angiotensin I-converting enzyme gene insertion/deletion polymorphism is associated with the severity of atherosclerosis

Background: Angiotensin II is produced primarily by angiotensin I-converting enzyme (ACE) within atherosclerotic lesions and ACE level in plaques correlates with the severity of vessel wall damage. Therefore, we investigated the possible association of ACE gene insertion/deletion (I/D) polymorphism and the severity of atherosclerosis, estimated on the basis of the number of coronary stenoses and critical arterial occlusions observed during coronary angiography. Methods: The study cohort included 172 patients with angiographically confirmed premature coronary artery disease. The ACE gene I/D polymorphism was genotyped using a PCR method. Results: The frequencies of DD genotype, D allele carrier-state (DD+ID genotypes) and the D allele increased with the number of stenoses in coronary vessels. D allele carriers (DD+ID genotypes) were more frequent in the subgroup of patients with stenoses in at least four coronary vessels than in other patients including subjects with one-, two- and three-vessel disease (97.4% vs. 74.4%, OR= 13.05, 95% CI: 1.81-100.00, chi(2) =9.84, p=0.0017). Furthermore, the D allele was significantly more frequent in patients with critical arterial occlusions (>90%) than in subjects without critical stenoses (61.1% vs. 49.3%, chi(2) = 9.84, p = 0.023). Conclusions: The ACE I/D polymorphism influences individual differences in severity of coronary artery disease and the D allele promotes generation of numerous and critical atherosclerotic lesions.