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

Abstract

BackgroundThe 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.MethodsBased 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.ResultsOur 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.ConclusionsThe meta-analysis indicated that eNOS gene 4b/a, T-786C, G894T polymorphism might be associated with IS.

Clinical Relevance of MTHFR, eNOS, ACE, and ApoE Gene Polymorphisms and Serum Vitamin Profile among Malay Patients with Ischemic Stroke

“…Recently, meta-analyses have reported the significant association between eNOS 4a/b polymorphism and increased risk of ischemic stroke, particularly in Asian population rather than Caucasian population. [34][35][36][37] Lower nitric oxide plasma level was detected among 4a allele carriers than in the 4b wild-type allele. 31 A similar trend found in genotype-phenotype studies on NOS protein concentration and enzyme activity, indicates that protein expression and enzyme activity were lower in 4a4b genotype as compared to 4b4b genotype.…”

<b><i>NOS3</i></b> 894G>T Polymorphism is Associated With Progression of Kidney Disease and Cardiovascular Morbidity in Type 2 Diabetic Patients: <b><i>NOS3</i></b> as a Modifier Gene for Diabetic Nephropathy?

“…Possible link between NOS3 894G>T and cardiovascular morbidity and mortality has been widely studied, unfortunately, most studies published so far were performed on non-Caucasian populations. Four recent meta-analyses found association of NOS3 SNP with ischemic stroke [30,31,32] or coronary heart disease [33] in Asian populations. No such association was found for Caucasian population.…”

Investigation of the relationship between ischemic stroke and endothelial nitric oxide synthase gene polymorphisms [G894T, intron 4 VNTR and T786C]

“…According to some metaanalyses, no significant differences exist between the Asian and Caucasian populations in terms of the T786C genotypes and allele distributions (Table 3) [6,10]. However, in a contrasting metaanalysis reported by Wang et al [17], the predominance of the C allele of the T-786C polymorphism was highlighted in Asians, indicating a significant protective effect against the risk of ischemic stroke in the codominant models (C vs T for T-786C) ( Table 3) [17]. In our study, we also observed that the C alleles and TC heterozygote polymorphism genotype were significantly lower in the patient group (with the possibility of a protective effect) in the Anatolian population (Tables 2 and 3).…”