Association between the ACE I/D polymorphism and risk of ischemic stroke: An updated meta-analysis of 47,026 subjects from 105 case–control studies

• We report the current totality of evidence on ACE I/D polymorphism and IS risk.
• ACE I/D polymorphism is confirmed as a risk factor for IS.
• This study may enrich studies on the identification of genetic variations of IS risk.
• This study may aid to find the theory for risk prediction, prevention, and therapy.

BackgroundThe association between the angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism and risk of ischemic stroke (IS) remains controversial and ambiguous. To clarify this association, a large meta-analysis was performed.MethodsElectronic databases in both English and Chinese were used to identify relevant studies (updated in February 2014). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to describe the strength of the association.ResultsOne hundred and fifty eligible studies, including 18,258 IS cases and 28,768 controls, were identified. Meta-analysis of these studies pointed to a significant association between the ACE I/D polymorphism and IS risk: (D vs. I: OR = 1.354, 95% CI = 1.272–1.440, P < 0.001; DD vs. II: OR = 1.755, 95% CI = 1.561–1.973, P < 0.001; ID vs. II: OR = 1.178, 95% CI = 1.098–1.263, P < 0.001; DD vs. ID/II: OR = 1.535, 95% CI = 1.399–1.684, P < 0.001; DD/ID vs. II: OR = 1.353, 95% CI = 1.251–1.463, P < 0.001). Subgroup analysis revealed a significantly elevated risk among Asians, but with borderline statistical significance among Caucasians.ConclusionThis meta-analysis indicated that the ACE I/D polymorphism may be a genetic susceptibility factor for IS, especially among Asians, but with borderline statistical significance for Caucasians. Further investigations are needed to validate our conclusions.