Endothelial NO Synthase Gene Polymorphisms and Risk of Ischemic Stroke in Asian Population: A Meta-Analysis

<div><p>Background</p><p>The association between polymorphism 4b/a, T-786C and G894T in endothelial NO synthase gene (eNOS) and ischemic stroke (IS) remains controversial in Asian. A meta-analysis was performed to better clarify the association between eNOS gene and IS risk.</p> <p>Methods</p><p>Based on the search of PubMed, Web of Science (ISI), CNKI (National Knowledge Infrastructure), Wan Fang Med Online and CBM (Chinese Biology Medical Literature Database) databases, all eligible case-control or cohort studies were identified. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) from fixed and random effect models were calculated. Heterogeneity among studies was evaluated using the I². Meta-regression was used to explore the potential sources of between-study heterogeneity. Begg's test was used to estimate publication bias.</p> <p>Results</p><p>Our study included 27 articles, contained 28 independent case–control studies, involved a total of 3,742 cases and 3,691 controls about 4b/a, 1,800 cases and 1,751 controls about T-786C and 2,747 cases and 2,872 controls about G894T. A significant association of 4a allele with increased risk of IS was found in dominant (FEM: OR = 1.498, 95% CI = 1.329–1.689), recessive (FEM: OR = 2.132, 95% CI = 1.383–3.286) and codominant (REM: OR = 1.456, 95% CI = 1.235–1.716) models. For T-786C and G894T, there were significant associations with dominant and codominant genetic models, but not with recessive genetic model.</p> <p>Conclusions</p><p>The meta-analysis indicated that eNOS gene 4b/a, T-786C, G894T polymorphism might be associated with IS.</p> </div

Subgroup analysis on the relation of BDNF gene rs6265 and rs2030324polymorphism with AD in codominant model.

<p>Abbreviations: FEM, fixed-effects model; REM, random-effects model. EOAD, early-onset Alzheimer’s Disease; LOAD, late-onset Alzheimer’s Disease.</p><p>rs6265: Codominant model, A vs. G; rs2030324: Codominant model, T vs C.</p

Main characteristics of BDNF gene rs6265 polymorphism genotype distributions in studies included in this meta-analysis.

*<p>The cases of these studies are late-onset Alzheimer’s disease (LOAD); Abbreviations: Na, not available; HWE, Hardy-Weinberg equilibrium. NINCDS-ADRDA, National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association criteria; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition); CERAD, Consortium to Establish a Registry for Alzheimer’s disease.</p

Characteristics of eNOS gene 4b/a polymorphism genotype distributions in studies included in this meta-analysis.

*<p>Studies deviated from the Hardy-Weinberg equilibrium</p

Meta-analysis for IS risk depending on the T-786C polymorphism in the eNOS gene.

<p>Forest plots of relationship between eNOS gene T-786C polymorphism and IS risk in codominant model in Asian. White diamond denotes the pooled OR. Black squares indicate the OR in each study, with square sizes inversely proportional to the standard error of the OR. Horizontal lines represent 95% CIs.</p

Flow diagram of literature search.

<p>Flow diagram of literature search.</p

Flow chart of meta-analysis for exclusion/inclusion of studies.

<p>Flow chart of meta-analysis for exclusion/inclusion of studies.</p

Characteristics of eNOS gene T-786C polymorphism genotype distributions in studies included in this meta-analysis.

<p>Characteristics of eNOS gene T-786C polymorphism genotype distributions in studies included in this meta-analysis.</p

Forest plots of relationship between BDNF gene rs6265 polymorphism and AD risk in codominant model (A vs. G) for female group.

<p>White diamond donates the pooled OR. Black squares indicate the OR in each study, with square sizes inversely proportional to the standard error of the OR. Horizontal lines represent 95% CIs.</p

Forest plots of relationship between BDNF gene rs6265 polymorphism and AD risk in codominant model (A vs. G) for overall analysis.

<p>White diamond donates the pooled OR. Black squares indicate the OR in each study, with square sizes inversely proportional to the standard error of the OR. Horizontal lines represent 95% CIs.</p