Many studies have investigated the association between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and risk of ischemic stroke. However, the evidence is inadequate to draw robust conclusions because most studies were generally small and conducted in heterogeneous populations. To shed light on these inconclusive findings, we conducted a large meta-analysis of studies relating the ACE I/D polymorphism to the risk of ischemic stroke.

Relevant studies were identified by searching PubMed and Embase through February 2012 and by reviewing the references of retrieved articles. We included studies that reported odds ratio (OR) with 95% confidence interval (CI) for the association between this polymorphism and ischemic stroke risk.

Fifty independent publications, with 10 070 stroke cases and 22 103 controls, were included. The results indicated that the DD homozygote carriers had a 37% higher risk of ischemic stroke when compared with the homozygotes II and heterozygote ID [odds ratio (OR) = 1.37, 95% confidence interval (CI): 1.22–1.53]. Subgroup analyses indicated that this higher risk was more pronounced among Asians, hospital-based studies, and small vessel disease (SVD). Potential publication bias may exist, but correction for this bias using a formal statistical method did not materially alter the combined risk estimate.

The results of our meta-analysis indicate that the D allele of ACE I/D polymorphism is a low-penetrance susceptibility marker of ischemic stroke.