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Endothelial nitric oxide synthase tagging single nucleotide polymorphisms and recovery from aneurysmal subarachnoid hemorrhage.

Abstract
Aneurysmal subarachnoid hemorrhage (SAH) is a hemorrhagic stroke subtype with a poor recovery profile. Cerebral vasospasm (CV), a narrowing of the cerebral vasculature, significantly contributes to the poor recovery profile. Variation in the endothelial nitric oxide (NO) synthase (eNOS) gene has been implicated in CV and outcome after SAH. The purpose of this project was to explore the potential association between three eNOS tagging single nucleotide polymorphisms (SNPs) and recovery from SAH. We included 195 participants with a diagnosis of SAH and DNA and 6-month outcome data available but without preexisting neurologic disease/deficit. Genotyping was performed using an ABI Prism 7000 Sequence Detection System and TaqMan assays. CV was verified by cerebral angiogram independently read by a neurosurgeon on 118 participants. Modified Rankin Scores (MRS) and Glasgow Outcome Scale (GOS) scores were collected 6 months posthemorrhage. Data were analyzed using descriptive statistics, analysis of variance (ANOVA) and chi-square analysis as appropriate. The sample was primarily female (n=147; 75.4%) and White (n=178; 91.3%) with a mean age of 54.6 years. Of the participants with CV data, 56 (47.5%) developed CV within 14 days of SAH. None of the SNPs individually were associated with CV presence; however, a combination of the three variant SNPs was significantly associated with CV (p=.017). Only one SNP (rs1799983, variant allele) was associated with worse 6-month GOS scores (p<.001) and MRS (p<.001). These data indicate that the eNOS gene plays a role in the response to SAH, which may be explained by an influence on CV.
AuthorsSheila Alexander, Samuel Poloyac, Leslie Hoffman, Matthew Gallek, Dianxu Ren, Jeffrey Balzer, Amin Kassam, Yvette Conley
JournalBiological research for nursing (Biol Res Nurs) Vol. 11 Issue 1 Pg. 42-52 (Jul 2009) ISSN: 1099-8004 [Print] United States
PMID19419976 (Publication Type: Journal Article)
Chemical References
  • Nitric Oxide Synthase Type III
Topics
  • Analysis of Variance
  • Cerebral Angiography
  • Chi-Square Distribution
  • Clinical Nursing Research
  • Female
  • Genetic Predisposition to Disease (genetics)
  • Genotype
  • Glasgow Outcome Scale
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide Synthase Type III (genetics)
  • Pennsylvania (epidemiology)
  • Polymorphism, Single Nucleotide (genetics)
  • Prospective Studies
  • Recovery of Function (genetics)
  • Risk Factors
  • Subarachnoid Hemorrhage (complications, diagnosis, genetics, rehabilitation)
  • Time Factors
  • Vasospasm, Intracranial (diagnostic imaging, epidemiology, genetics)

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