Association between Angiotensin Converting Enzyme Insertion/Deletion gene polymorphism with the risk of Hemorrhagic Stroke: A systematic review and Meta-Analysis of 53 studies

• Published in: Gene Vol. 790; p. 145696
• Main Authors: Nath, Manabesh, Misra, Shubham, Talwar, Pumanshi, Vibha, Deepti, Srivastava, Achal Kumar, Prasad, Kameshwar, Kumar, Pradeep
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.07.2021
• Subjects: Angiotensin Converting Enzyme; biomarkers; blood pressure; confidence interval; genes; Hemorrhagic stroke; homeostasis; Meta-analysis; mortality; odds ratio; risk; Single Nucleotide Polymorphisms; statistical analysis; stroke; systematic review; USA; OR; ACE; CI; Hemorrhagic stroke; RAAS; Angiotensin Converting Enzyme; PRISMA; Single Nucleotide Polymorphisms; PCR-RFLP; HS; HV; ICH; Meta-analysis; PB; NA; NOS; aSAH; UK; CNKI; HWE; IA; HB; I/D
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2021.145696

•Hemorrhagic stroke (HS) results in significant mortality and disability worldwide.•Angiotensin Convertase Enzyme (ACE) is responsible for blood pressure regulation and vascular homeostasis.•Pooled analyses of 53 studies showed that ACE I/D gene polymorphism had significant association with risk of HS in overall study population.•Subgroup analyses further revealed significant relationship of ACE I/D polymorphism with ICH in Asians but not in Caucasians population under recessive model. 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. 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 I2 < 50%) or random effect (when I2 > 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. 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). 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.