title: Impact of High-Mobility Group Box 1 Polymorphism on Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.
abstract: OBJECTIVE
  The high-mobility group box 1 (HMGB1) protein is a eukaryotic, ubiquitously expressed protein that serves as a biomarker for various diseases and is involved in the promotion of a proinflammatory response to cell injury. In aneurysmal subarachnoid hemorrhage (aSAH), increased HMGB1 levels have been linked to poor outcome and an increased risk for cerebral vasospasm. The role of HMGB1 polymorphisms in aSAH has not been previously investigated.
  
  
  METHODS
  Patients with aSAH and controls enrolled in the prospective, 2-center CARAS (Cerebral Aneurysm Renin Angiotensin System) study were evaluated. The 3814 C/G HMGB1 single nucleotide polymorphism (SNP) rs2249825 was detected using 5'exonuclease (Taqman) genotyping assays from blood samples from patients with aSAH and controls. Associations between aSAH and its clinical sequelae with the HMGB1 SNP were assessed.
  
  
  RESULTS
  Samples from 149 patients with aSAH and 50 controls were available for analysis. No increased risk for aSAH associated with the SNP was found compared with the control group. Delayed cerebral ischemia (DCI) was defined as a cerebral infarction at the time of discharge from the intensive care unit and identified in 21.2% of patients with aSAH. In multivariable logistic regression analysis, the G allele of rs2249825 was independently associated with DCI (odds ratio, 5.695; 95% confidence interval, 1.804-17.975; P = 0.003).
  
  
  CONCLUSIONS
  The minor allele G of rs2249825 was associated with an increased risk for DCI, or cerebral infarction, after aSAH. This finding may be attributable to an increased HMGB1 protein expression in these patients.
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, Birmingham, Alabama, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Foreman
authors.affiliation: Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Harrigan
authors.affiliation: Department of Neurosurgery, University of Alabama at Birmingham, 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, 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, Birmingham, Alabama, USA.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Pittet
authors.affiliation: Department of Anesthesiology, University of Alabama at Birmingham, 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; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D024243:HMGB1 Protein / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein; C585491:HMGB1 protein, human
keywords: Aneurysm; Delayed cerebral ischemia; High-mobility group box 1; Outcome; Polymorphism; Subarachnoid hemorrhage