Endothelial NO synthase gene polymorphisms and risk of ischemic stroke: A meta-analysis

Tao, Hong-miao; Chen, Guozhong

doi:10.1016/j.neures.2009.04.001

Cited by 26 publications

(23 citation statements)

References 36 publications

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“…Studies suggest that eNOS is most likely to synthesize the NO that is responsible for maintaining resting cerebral blood flow [9]. The participation of the eNOS gene in the physiology of the vasculature makes it a biologically plausible candidate for study as a susceptibility gene for ischemic stroke [10].…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Jiang

et al. 2013

PLoS ONE

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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.

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Section: Introductionmentioning

confidence: 99%

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

Wang

Jiang

et al. 2013

PLoS ONE

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“…Relatively small studies have shown variable associations between individual NOS3 variants and NOS3 haplotypes with the risk of stroke (Howard et al, 2005;Majumdar et al, 2010;Saidi et al, 2010;Song et al, 2010;Yemisci et al, 2009). A meta-analysis of casecontrolled studies through 2008 examining the 894G > T and 27-bp VNTR variants of NOS3 in stroke suggested that the 4a allele was not associated with an increased risk, but that the 894T allele may have a marginally increased risk of stroke (odds ratio 1.14; 95% CI 0.99,1.31; Tao and Chen, 2009).…”

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confidence: 99%

Variants of the Endothelial Nitric Oxide Gene and Cerebral Blood Flow after Severe Traumatic Brain Injury

Robertson

Gopinath

Valadka

et al. 2011

Journal of Neurotrauma

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Experimental studies suggest that nitric oxide produced by endothelial nitric oxide synthase (NOS3) plays a role in maintaining cerebral blood flow (CBF) after traumatic brain injury (TBI). The purpose of this study was to determine if common variants of the NOS3 gene contribute to hypoperfusion after severe TBI. Fifty-one patients with severe TBI were studied. Cerebral hemodynamics, including global CBF by the stable xenon computed tomography (CT) technique, internal carotid artery flow volume (ICA-FVol), and flow velocity in intracranial vessels, were measured within 12 h of injury, and at 48 h after injury. A blood sample was collected for DNA analysis, and genotyping of the following variants of the NOS3 gene was performed: -786T > C, 894G > T, and 27bp VNTR. Cerebral hemodynamics were most closely related to the -786T > C genotype. CBF averaged 57.7 -3.0 mL/100 g/min with the normal T/T genotype, 47.0 -2.5 mL/100 g/min with the T/C, and 37.3 -8.8 mL/100 g/min with the C/C genotype ( p = 0.0146). Cerebrovascular resistance followed an inverse pattern with the highest values occurring with the C/C genotype ( p = 0.0027). The lowest ICA-FVol of 124 -43 mL/min was found at 12 h post-injury in the more injured hemisphere of the patients with the C/C genotype ( p = 0.0085). The mortality rate was 20% in patients with the T/T genotype and 17% with the T/C genotype. In contrast, both of the patients with the C/C genotype were dead at 6 months post-injury ( p = 0.022). The findings in this study support the importance of NO produced by NOS3 activity in maintaining CBF after TBI, since lower CBF values were found in patients having the -786C allele. The study suggests that a patient's individual genetic makeup may contribute to the brain's response to injury and determine the patient's chances of surviving the injury. The results here will need to be studied in a larger number of patients, but could explain some of the variability in outcome that occurs following severe TBI.

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“…Since it has an important role in the physiology of the vasculature, genetic variation could alter the expression and activity of eNOS, and therefore contribute to the development of stroke. A meta-analysis [16] published in 2009 suggested, TT genotype of G-894T polymorphism has no association with ischemic stroke (OR, 1.14; 95% CI, 0.99 to 1.31). A recent meta-analysis included 27 studies suggest the positive association between eNOS gene 4b/a, T-786C, G894T polymorphism and ischemic stroke [17].…”

Section: Introductionmentioning

confidence: 99%

Identification of genetic contribution to ischemic stroke by screening of single nucleotide polymorphisms in stroke patients by using a case control study design

et al. 2013

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BackgroundStroke is the second most common cause of death and disability worldwide. It is a multi-factorial disease influenced by both environmental and genetic factors. Studies from the different ethnic regions of world have reported variable results on association of Apolioprotein E (APOE), Methylenetetrahydrofolate reductase (MTHFR), Endothelial Nitric Oxide Synthase (ENOS), Factor V Leiden (F5), Cytochrome P450 4F2 (CYP4F2), beta-fibrinogen and Phosphodiesterase 4D (PDE4D) gene in stroke. There has been substantial evidence from the European descent genetic studies showing that genetic risk of stroke varies as per specific subtypes of ischemic stroke.This study aims to test the hypothesis that above mentioned encoding gene polymorphisms are associated with stroke and to determine whether risk varies as per specific subtypes of stroke.Methods/DesignThe study design would be case–control study. Six hundred cases with diagnosis of stroke and 600 age and sex matched controls will be recruited. Controls will be matched in 1:1 ratio. Baseline and demographic data will be collected in standardized data collection form. Four ml of blood will be collected in EDTA coated vial and will be used for DNA isolation. Genotyping will be done by using PCR-RFLP method. For the reconfirmation of RFLP results, PCR product of each genotype in triplet for all the selected polymorphism will be sent for DNA sequencing. Data will be analyzed using conditional logistic regression to determine odds ratio associated with the above genes.DiscussionThis protocol will assess the association of above mentioned gene polymorphisms with ischemic stroke in North Indian Population. This study will also helpful to determine genetic component of stroke and whether variation in genetic risk as per different subtypes of stroke.

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Endothelial NO synthase gene polymorphisms and risk of ischemic stroke: A meta-analysis

Cited by 26 publications

References 36 publications

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

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

Variants of the Endothelial Nitric Oxide Gene and Cerebral Blood Flow after Severe Traumatic Brain Injury

Identification of genetic contribution to ischemic stroke by screening of single nucleotide polymorphisms in stroke patients by using a case control study design

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