Meta-analysis Of Angiotensin Converting Enzyme (I/D) Polymorphism In Cerebral Small Vessel Disease

Objectives There is conflicting evidence regarding a possible association between angiotensin converting enzyme(ACE I/D) polymorphism and cerebral small vessel disease(CSVD). We aimed to evaluate the relationship between ACE polymorphism and cerebral small vessel disease by performing a systematic review and meta-analysis of available studies.Methods The relevant studies were identified by searching the PubMed, Google, CNKI,CBMs, YIZHI, WANFANG and WEIPU databases from 1995 to 2015. 26 cohort studies were selected for analysis based on comprehensive quality assessment using a standardized scale. The odds ratio(OR) and corresponding 95% confidence intervals(CIs)for CSVD risk associated with this polymorphism were estimated using a fixed-effect or random-effect model. Heterogeneity was evaluated by the Q value and I2 statistic. The visual funnel plots were used to assess possible publication bias.Results There was a statistical association of the ACE(I/D) polymorphism with CSVD risk in(DD+ID/II): OR=1.30, 95%CI(1.11,1.52), P=0.001;(DD/ID+II): OR=1.44, 95%CI(1.19,1.75), P=0.0002;(DD/II): OR=1.59, 95%CI(1.26,1.99), P<0.0001,(ID/II):OR=1.16, 95%CI(1.02,1.32),P=0.02;(D/I):OR=1.30,95%CI(1.15,1.48), P<0.0001. As we stratified according to CSVD subtype and ethnicity, we found similar results for respective subgroups.Conclusions This meta-analysis suggests that the ACE(I/D) polymorphism may be a risk factor for CSVD, the DD genotype and D allele may increase the risk of CSVD.Subgroup analysis suggests this genetic liability is associated with lacunar infarcts and white matter hyperintensities in both Asian and Caucasian, respectively.