title: Endothelial nitric oxide synthase gene single-nucleotide polymorphism predicts cerebral vasospasm after aneurysmal subarachnoid hemorrhage.
abstract: Vasospasm is a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). Studies have shown a link between single-nucleotide polymorphisms (SNPs) in the endothelial nitric oxide synthase (eNOS) gene and the incidence of coronary spasm and aneurysms. Alterations in the eNOS T-786 SNP may lead to an increased risk of post-aSAH cerebral vasospasm. In this prospective clinical study, 77 aSAH patients provided genetic material and were followed for the occurrence of vasospasm. In multivariate logistic regression analysis, genotype was the only factor predictive of vasospasm. The odds ratio (OR) for symptomatic vasospasm in patients with one T allele was 3.3 (95% confidence interval (CI): 1.1 to 10.0, P=0.034) and 10.9 for TT. Patients with angiographic spasm were 3.6 times more likely to have a T allele (95% CI: 1.3 to 9.6, P=0.013; for TT: OR 12.6). Patients with severe vasospasm requiring endovascular therapy were more likely to have a T allele (OR 3.5, 95% CI: 1.3 to 9.5, P=0.016; for TT: OR 12.0). Patients with the T allele of the eNOS gene are more likely to have severe vasospasm. Presence of this genotype may allow the identification of individuals at high risk for post-aSAH vasospasm and lead to early treatment and improved outcome.
authors.affiliation: Department of Neurological Surgery, Columbia University, New York, New York, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Starke
authors.forename: Grace H
authors.initials: GH
authors.lastname: Kim
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Komotar
authors.forename: Zachary L
authors.initials: ZL
authors.lastname: Hickman
authors.forename: Eric M
authors.initials: EM
authors.lastname: Black
authors.forename: Maritza B
authors.initials: MB
authors.lastname: Rosales
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Kellner
authors.forename: David K
authors.initials: DK
authors.lastname: Hahn
authors.forename: Marc L
authors.initials: ML
authors.lastname: Otten
authors.forename: John
authors.initials: J
authors.lastname: Edwards
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: James J
authors.initials: JJ
authors.lastname: Russo
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Mayer
authors.forename: Edward S
authors.initials: ES
authors.lastname: Connolly
mesh_terms: D000783:Aneurysm / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020301:Vasospasm, Intracranial / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics
chemical_list: D052250:Nitric Oxide Synthase Type III