Association Between Angiotensin Converting Enzyme Insertion/Deletion Gene Polymorphism with the Risk of Hemorrhagic Stroke: A Systematic Review and Meta-Analysis of 53 Studies

Background And Aims: Hemorrhagic stroke (HS) results in significant mortality and disability worldwide. Angiotensin Converting Enzyme (ACE) is responsible for blood pressure regulation and vascular homeostasis. Our objective was to conduct a comprehensive meta-analysis for ascertaining the association of ACE I/D polymorphism with HS since a number of studies depicted inconclusive evidence.

Methods: Literature search was performed till July 10, 2020 in PubMed, EMBASE, Cochrane, Chinese National Knowledge Information and Google Scholar databases with keywords: ('Angiotensin Converting Enzyme' OR 'ACE') AND ('Single Nucleotide polymorphisms' OR 'SNP') AND ('Hemorrhagic stroke or 'HS'). Pooled Odds Ratio (OR) and 95% Confidence Interval (CI) were determined for gene-disease association using either fixed (when I < 50%) or random effect (when I > 50%) models. Risk of bias in studies was assessed using funnel plots and sensitivity analyses. Statistical analysis was performed using STATA version 13.0 software.

Results: A total of 53 studies having 5186 HS and 7347 healthy control subjects were included in our meta-analysis. Pooled analyses showed that ACE I/D gene polymorphism had significant association with risk of HS in overall study population [(dominant model: OR = 1.29, 95% CI = 1.12-1.50 & recessive model: OR = 1.79, 95% CI = 1.46-2.20)]. Population subgroup analyses further revealed significant relationship of ACE I/D polymorphism with ICH in Asians (recessive: OR 1.97, 95% CI = 1.57-2.47) but not in Caucasians (recessive: OR 1.02, 95% CI = 0.76-1.36).

Conclusion: This meta-analysis suggests that ACE I/D polymorphism may lead to risk of HS and can be a potential biomarker for HS susceptibility especially in Asian population.