The angiotensin converting enzyme insertion/deletion polymorphism and intracranial aneurysm: A meta-analysis of case-control studies

Abstract

Previous studies investigating the association between angiotensin converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and intracranial aneurysm (IA) have provided inconsistent results and no large systematic review or meta-analyses have been conducted regarding this issue. To confirm whether the ACE I/D polymorphism correlates with risk of IA. We conducted a meta-analysis to increase the statistical power by using all the available published data. Two investigators independently searched the PubMed, Medline, Embase, China National Knowledge Infrastructure and Chinese Biomedicine Databases for studies published before December 2012. For included studies, we performed meta-analyses using the Cochrane RevMan software. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for ACE I/D polymorphisms and IA were calculated in a fixed-effects model or a random-effects model when appropriate. We used Cochran's Q statistic and the I 2 statistic to assess heterogeneity and funnel plot to assess potential publication bias. We also carried out stratified analyses and sensitivity analyses by ethnicity, country and source of control group, sample size and Hardy-Weinberg equilibrium (HWE) in controls. Six eligible studies were reviewed and analyzed, involving 854 cases and 1280 controls. Overall, compared with D allele, there was a close relationship between I allele and IA risk (OR: 1.21, 95% CI: 1.07-1.37, P = 0.003; P(heterogeneity) = 0.56; I² = 0%). ACE I+ (I/I and I/D) genotype had significantly increased risk for IA (OR: 1.27, 95% CI: 1.03-1.57, P = 0.03; P(heterogeneity) = 0.14; I² = 40%). This association remained consistently strong when analyses were limited to studies, in which genotype frequencies were in HWE. No publication bias was found in the present study. Our meta-analysis suggests, there is a close relationship between ACE I/D polymorphism and IA risk. Since limited studies and subjects were included, it is critical that larger and especially well-designed multicentric studies, which based on interactions of ACE and different confounding factors should be performed to re-evaluate the association.