Association of Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism with the Risk of Atherosclerosis

Aims: The objective of this study was to perform a meta-analysis to evaluate the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and susceptibility to atherosclerosis (AS). Methods: MEDLINE, EMBASE, and the ISI Web of Science were searched for all eligible published studies concerning the relationship of ACE gene polymorphism with AS without language restrictions. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate this relationship under different genetic models using meta-analytic methods. Results: A total of 15 articles (16 studies) were involved in this meta-analysis. The D allele of the ACE gene had a nonsignificant increase in the risk of AS (D versus I: OR = 1.23, 95% CI,.98-1.53, P = .07; I² = 87.2%, P_{heterogeneity} < .01). Compared with the II genotype, the DI (relative risk [RR]: 1.35, 95% CI: 1.09, 1.67, P < .01; I² = 47.8%, P_{heterogeneity} = .017) and (DD + DI) (RR = 1.38, 95% CI: 1.04, 1.82, P = .02; I² = 73.3%, P_{heterogeneity} < .01) genotype of ACE was associated with higher risk of AS, respectively. Subjects with the DD genotype showed a statistically nonsignificant trend toward greater risk of AS (RR = 1.53, 95% CI: .97, 2.43, P = .07; I² = 88.6%, P_{heterogeneity} < .01). Further subgroup analyses showed that significant relationships were only found in Europeans under different gene polymorphism or different genotype models rather than Asians. Conclusions: The present meta-analysis indicated that the D allele in the ACE gene was associated with the risk of AS, especially in Europeans. Furthermore, increased copy number of D allele was significantly associated with increased AS risk in a dose-dependent manner.