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Endothelial nitric oxide synthase polymorphism (-786T->C) and increased risk of angiographic vasospasm after aneurysmal subarachnoid hemorrhage.

ABSTRACT: Vasospasm after aneurysmal subarachnoid hemorrhage (SAH) remains a leading cause of death and disability after aneurysm rupture. Decreased availability of nitric oxide (NO) may be crucial in its pathogenesis. We hypothesized that endothelial NO synthase (eNOS) polymorphisms may determine susceptibility to vasospasm in SAH patients.We conducted a prospective cohort study of SAH patients and determined vasospasm by cerebral angiography. We genotyped 3 eNOS polymorphisms: an intron 4 variable-number tandem-repeat, a promoter single-nucleotide polymorphism (-786T-->C SNP), and a coding SNP in exon 7 (894G-->T encoding E298D). Using multivariable logistic regression, we quantified the association of eNOS polymorphisms in patients with vasospasm confirmed by cerebral angiography.For the eNOS promoter -786T-->C SNP, the presence of the CC genotype compared with any T genotype (CT or TT) was associated with increased odds of vasospasm (odds ratio=2.97, 95% CI=1.32 to 6.67, P=0.008). No association with vasospasm was observed for the eNOS 894G-->T or variable-number tandem-repeat polymorphisms.These findings suggest that genetic variation influencing NO regulation contributes to the risk of angiographic vasospasm in patients with SAH. The specific role of the promoter SNP (-786T-->C) may determine the effect of NO regulated by this pathway, distinct from other known eNOS polymorphisms.

SUBMITTER: Ko NU

PROVIDER: S-EPMC2650384 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Endothelial nitric oxide synthase polymorphism (-786T->C) and increased risk of angiographic vasospasm after aneurysmal subarachnoid hemorrhage.

Ko Nerissa U NU Rajendran Pam P Kim Helen H Rutkowski Martin M Pawlikowska Ludmila L Kwok Pui-Yan PY Higashida Randall T RT Lawton Michael T MT Smith Wade S WS Zaroff Jonathan G JG Young William L WL

Stroke 20080228 4

<h4>Background and purpose</h4>Vasospasm after aneurysmal subarachnoid hemorrhage (SAH) remains a leading cause of death and disability after aneurysm rupture. Decreased availability of nitric oxide (NO) may be crucial in its pathogenesis. We hypothesized that endothelial NO synthase (eNOS) polymorphisms may determine susceptibility to vasospasm in SAH patients.<h4>Methods</h4>We conducted a prospective cohort study of SAH patients and determined vasospasm by cerebral angiography. We genotyped 3 ...[more]

PMID: 18309169

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Project description:IntroductionCerebral vasospasm (CVS) is the most common neurological complication after aneurysmal subarachnoid hemorrhage (aSAH) and associated with poor functional outcome and mortality. Reports on incidence and predictors of CVS in Chinese patients with aSAH were scarce. We aimed to estimate the incidence and predictors of angiographic vasospasm (AV), symptomatic vasospasm (SV), and cerebral infarction in Chinese patients with aSAH.MethodsWe retrospectively reviewed the medical records of 542 consecutive aSAH patients admitted to neurosurgery department of the First Affiliated Hospital of Xinjiang Medical University in Urumqi city of China between January 1, 2011 and December 31, 2015. AV, SV and cerebral infarction were defined based on clinical data and neuroimaging findings. Univariate and multivariate analyses were performed to identify predictors of AV, SV or cerebral infarction.Results343 (63.3%) patients fulfilled the inclusion and exclusion criteria. Of them, 182(53.1%) developed AV, 99 (28.9%) developed SV, and 87 (25.4%) developed cerebral infarction. A history of hypertension, poor modified Fisher grade (3-4) and poor Hunt-Hess grade (4-5) on admission were common risk factors for AV, SV and cerebral infarction. Patients from Uyghur ethnic group or other minorities were less likely to develop AV, SV or cerebral infarction, compared to those from Han ethic group after adjustment of other potential confounders. Additionally, age ≥53 years, leukocyte count ≥11× 109/L on admission and being current or former smokers were independent risk factors of cerebral infarction. Leukocyte count ≥11× 109/L on admission and aneurysm size ≥ 10 mm were independent risk factors of SV. Serum glucose level ≥7.0 mmol/L on admission was an independent risk factor of AV.ConclusionRisk factors of different definitions of CVS were diverse in Chinese patients with aSAH; however, risk factors of SV and cerebral infarction seem to be similar. We recommend early and aggressive therapy in these patients at-risk of CVS.

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Endothelial nitric oxide synthase polymorphism (-786T->C) and increased risk of angiographic vasospasm after aneurysmal subarachnoid hemorrhage.

Publications

Endothelial nitric oxide synthase polymorphism (-786T->C) and increased risk of angiographic vasospasm after aneurysmal subarachnoid hemorrhage.

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