title: Endothelial Nitric Oxide Synthase Polymorphism Is Associated with Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage.
abstract: OBJECTIVE
  Nitric oxide is critical in the regulation of cerebral blood flow and smooth muscle proliferation. It is synthesized by 3 nitric oxide synthase (NOS) isoforms: neuronal, inducible, and endothelial NOS (eNOS). Aneurysmal subarachnoid hemorrhage (aSAH) causes endothelial dysfunction that, in turn, contributes to pathophysiologic processes surrounding aSAH. Previous studies reported an association of an eNOS single nucleotide polymorphism (SNP) with the clinical sequelae of aSAH. Here, we further elucidate the impact of this eNOS SNP on the clinical course after aSAH.
  
  
  METHODS
  The Cerebral Aneurysm Renin Angiotensin System study prospectively enrolled aSAH patients at 2 academic institutions in the United States from 2012-2015. Blood samples from all patients enrolled in the study were used for genetic evaluation using 5'exonuclease (Taqman) genotyping assays. Associations between the eNOS SNP rs2070744 (786 T->C) and clinical course after aSAH were analyzed.
  
  
  RESULTS
  Samples from 149 aSAH patients were available for analysis. The C allele of the eNOS SNP independently predicted an increased risk for delayed cerebral ischemia (OR = 2.936, 95% CI 1.048-8.226, P = 0.040). The eNOS SNP rs2070744 was not associated with functional outcome or size of aneurysm at the time of rupture.
  
  
  CONCLUSIONS
  The present study is the first to demonstrate that the C allele of the eNOS SNP 786 T->C rs2070744 is independently associated with an increased risk for delayed cerebral ischemia following aSAH.
authors.affiliation: Department of Neurosurgery, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg/Saar, Germany. Electronic address: hendrix.philipp@gmail.com.
authors.forename: Philipp
authors.initials: P
authors.lastname: Hendrix
authors.affiliation: Department of Neurosurgery, University of Alabama at Birmingham, Alabama, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Foreman
authors.affiliation: Department of Neurosurgery, University of Alabama at Birmingham, Alabama, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Harrigan
authors.affiliation: Department of Neurosurgery, University of Alabama at Birmingham, Alabama, USA.
authors.forename: Winfield S
authors.initials: WS
authors.lastname: Fisher
authors.affiliation: Department of Neurosciences, Inova Health System, Falls Church, Virginia, USA.
authors.forename: Nilesh A
authors.initials: NA
authors.lastname: Vyas
authors.affiliation: Department of Neurosciences, Inova Health System, Falls Church, Virginia, USA; Department of Molecular Neuroscience, George Mason University, Fairfax, Virginia, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lipsky
authors.affiliation: Department of Molecular Neuroscience, George Mason University, Fairfax, Virginia, USA.
authors.forename: Minkuan
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, University of Alabama at Birmingham, Alabama, USA; Department of Neurosciences, Inova Health System, Falls Church, Virginia, USA; Department of Molecular Neuroscience, George Mason University, Fairfax, Virginia, USA.
authors.forename: Beverly C
authors.initials: BC
authors.lastname: Walters
authors.affiliation: Seattle Science Foundation, Seattle, Washington, USA.
authors.forename: R Shane
authors.initials: RS
authors.lastname: Tubbs
authors.affiliation: Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammadali M
authors.initials: MM
authors.lastname: Shoja
authors.affiliation: Department of Anesthesiology, University of Alabama at Birmingham, Alabama, USA.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Pittet
authors.affiliation: Department of Anesthesiology, University of Alabama at Birmingham, Alabama, USA.
authors.forename: Mali
authors.initials: M
authors.lastname: Mathru
authors.affiliation: Neurosurgical Service, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA; Department of Neurosurgery, Geisinger Health System, Danville, Pennsylvania, USA.
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Griessenauer
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002545:Brain Ischemia / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D013997:Time Factors
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: Aneurysm size; Delayed cerebral ischemia; Endothelial nitric oxide synthase; Polymorphism; Subarachnoid hemorrhage; Vasospasm; eNOS; eNOS SNP 786 T->C