title: Ryanodine Receptor 1 Polymorphism Is Not Associated with Aneurysmal Subarachnoid Hemorrhage or its Clinical Sequelae.
abstract: OBJECTIVE
  The pathophysiologic mechanisms underlying cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) remain poorly understand. Ryanodine receptors (RYR) are intracellular calcium channels involved in the regulation of vascular smooth muscle cells and cerebrovascular tone and diameter. Previous work reported an association between an RYR polymorphism and cerebral vasospasm. Here, we sought to assess the impact of that RYR polymorphism on aSAH and its clinical sequelae.
  
  
  METHODS
  Blood samples from all patients enrolled in the CARAS (Cerebral Aneurysm Renin Angiotensin System) study were used for genetic evaluation. The RYR1 single nucleotide polymorphism (SNP) rs35364374 was detected using 5'exonuclease (Taqman) genotyping assays. Associations between the RYR1 polymorphism and aSAH and its clinical sequelae were analyzed.
  
  
  RESULTS
  Samples from 149 patients with aSAH and 50 controls were available for analysis. Multivariable regression analysis did not show an association of RYR1 SNP rs35364374 with aSAH. Moreover, there was no association of RYR1 SNP rs35364374 with clinical vasospasm, delayed cerebral ischemia, functional outcome at discharge, or functional outcome at last follow-up.
  
  
  CONCLUSIONS
  Contrary to a previous report, the RYR1 SNP rs35364374 was not associated with aSAH or its clinical sequelae.
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: D002545:Brain Ischemia / Q000453:epidemiology* / Q000235:genetics*; D015984:Causality; D015897:Comorbidity; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D012307:Risk Factors; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D013345:Subarachnoid Hemorrhage / Q000453:epidemiology* / Q000235:genetics*; D014481:United States / Q000453:epidemiology; D020301:Vasospasm, Intracranial / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D019837:Ryanodine Receptor Calcium Release Channel
keywords: Aneurysm; Clinical vasospasm; Delayed cerebral ischemia; Functional outcome; Polymorphism; Ryanodine receptor; Subarachnoid hemorrhage