Association Between the Angiotensin-Converting Enzyme I/D Polymorphism and Risk of Cerebral Small Vessel Disease: A Meta-Analysis Based on 7186 Subjects

Abstract

Introduction: Cerebral small vessel disease (CSVD) causes a quarter of all strokes and is the most common pathology underlying vascular dementia. However, the mechanism of CSVD remains unclear. Numerous studies have investigated whether the angiotensin-converting enzyme (ACE) intersection/deletion (I/D) polymorphism influences the risk of CSVD, but the results are controversial.

Methods: We searched English and Chinese databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to examine the existence of genetic associations between the ACE I/D polymorphism and the risk of CSVD. All relevant studies were screened and meta-analyzed using Review Manager 5.4.

Results: A total of 27 studies involving 7,186 subjects were identified for the meta-analysis. The results of five genetic models showed a significantly increased risk of CSVD (allelic, OR=1.30; recessive, OR=1.41; dominant, OR=1.34; homozygous, OR=1.55 and heterozygous OR=1.22) in the overall analysis. Furthermore, in subgroup analysis, increased CSVD risks were also observed in Asian and Caucasian populations. We also found no relationship between ACE I/D and leukoaraiosis (LA) in patients with lacunar infarction (LI).

Conclusion: The ACE I/D polymorphism was positively associated with CSVD in both populations. However, this polymorphism did not increase the risk of LA in LI patients.

Keywords: ACE; Angiotensin-converting enzyme; CSVD; Cerebral small vessel disease; Meta-analysis; Polymorphism.