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Endothelial Nitric Oxide Synthase (eNOS) Gene Polymorphisms and Risk of Aneurysmal Subarachnoid Hemorrhage: An Updated Meta-Analysis

Author(s): N. Manabesh, M. Shubham, K. Amit, S. Rakhee, K. Pradeep

Previously published studies have examined whether the polymorphisms (G894T, 4b/a, and T786C) in the Endothelial Nitric Oxide Synthase (eNOS) gene are associated with risk of Aneurysmal Subarachnoid Hemorrhage (aSAH), have reported conflicting results. Thus, we performed a meta-analysis to examine the potential association between these three single nucleotide gene polymorphisms (SNPs) of eNOS gene and aSAH risk. A literature search was carried out for eligible candidate gene studies published before April 30, 2020 in the PubMed, EMBASE, Google Scholar and Trip databases. The strength of association between eNOS and G894T, 4b/a, and T786C gene polymorphisms was calculated by pooled Odds Ratios (ORs) with 95% Confidence Intervals (95%CIs) using either a fixed-effect model (I2<50%) or a random-effect model (I2>50%). Heterogeneity between studies was examined using influence diagnostics analysis and publication bias was evaluated using Begg’s funnel plots. All the statistical analyses were assessed using R version 3.6.2 software.13 case-control studies involving 2131 aSAH cases and 2223 controls were analyzed in our meta-analysis. In the overall analysis, no evidence of significant association for G894T (OR= 1.04; 95% CI: 0.89 to 1.23; p=0.52), T786C (OR= 1.16; 95% CI: 0.97 to 1.40, p=0.14) and 4b/a (OR= 1.17; 95% CI: 0.81 to 1.68, p<0.01) eNOS gene polymorphisms and N. Manabesh, et al. Genetics and Molecular Research 19 (5): gmr16039991 risk of aSAH was observed. Our comprehensive meta-analysis ascertains that G894T, T786C and 4b/polymorphisms of eNOS gene may not be associated with the risk of aSAH. Further prospective large epidemiological studies are required to substantiate these findings.