Angiotensin-converting enzyme insertion/deletion gene polymorphisms and risk of intracerebral hemorrhage: A meta-analysis of epidemiologic studies

Studies investigating the association between the intron 16 insertion/deletion (I/D) polymorphism (rs4646994) in the angiotensin-converting enzyme (ACE) gene and risk of intracerebral hemorrhage (ICH) have reported conflicting results. We here performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of this relationship. Published literature from the National Library of Medline and Embase databases were retrieved. Odds ratios (OR) and 95% confidence limits (CLs) were calculated in fixed- or random-effects models when appropriate. Subgroup analyses were performed by race. This meta-analysis included six case-control studies, which included 744 ICH cases and 1411 controls. The combined results based on all studies showed that ICH cases had a significantly lower frequency of ID genotype (OR (codominant model) = 0.43, 95% CL = 0.22, 0.84, p = 0.01). In the subgroup analysis by race, we found that ICH cases had a significantly lower frequency of II genotype in Asians (OR (recessive model) = 0.50, 95% CL = 0.38, 0.66, p < 0.001; OR (codominant model) = 0.25, 95% CL = 0.09, 0.71, p = 0.009). In conclusion, our meta-analysis suggests that ACE I/D polymorphisms are associated with ICH, especially in Asians.