title: Haptoglobin genotype and functional outcome after aneurysmal subarachnoid hemorrhage.
abstract: OBJECTIVE
  Haptoglobin allele heterogeneity has been implicated in differential reactive oxidant inhibition and inflammation. Haptoglobin α2-α2 has a lower affinity for binding hemoglobin, and when bound to hemoglobin, is cleared less easily by the body. The authors hypothesized that haptoglobin α2-α2 genotype should be less protective for downstream injury after aneurysmal subarachnoid hemorrhage (aSAH) and should portend a worse outcome.
  
  
  METHODS
  Patients with Fisher Grade 2 or higher aSAH were enrolled in the study. Genotyping for haptoglobin genotype was performed from blood and/or CSF. Demographic information, medical condition variables, and hospital course were abstracted from the medical record upon enrollment into the study. Outcome data (modified Rankin Scale score, Glasgow Outcome Scale score, and mortality) were collected at 3 months posthemorrhage.
  
  
  RESULTS
  The authors enrolled 193 patients who ranged in age from 18 to 75 years. Only Caucasians were used in this analysis to minimize bias from variable haptoglobin allele frequencies in populations of different ancestral backgrounds. The sample had more women than men (overall mean age 54.45 years). Haptoglobin α2 homozygotes were older than the other individuals in the study sample (57.27 vs 53.2 years, respectively; p = 0.02) and were more likely to have Fisher Grade 3 SAH (p = 0.02). Haptoglobin α2-α2 genotype, along with Fisher grade and Hunt and Hess grade, was associated with a worse 3-month outcome compared to those with the haptoglobin α1-α1 genotype according to modified Rankin Scale score after controlling for covariates (OR 4.138, p = 0.0463).
  
  
  CONCLUSIONS
  Patients with aSAH who carry the haptoglobin α2-α2 genotype had a worse outcome. Interestingly, the presence of a single α-2 allele was associated with worse outcome, suggesting that the haptoglobin α-2 protein may play a role in the pathology of brain injury following aSAH, although the mechanism for this finding requires further research. The haptoglobin genotype may provide additional information on individual risk of secondary injury and recovery to guide care focused on improving outcomes.
authors.affiliation: Department of Acute and Tertiary Care, School of Nursing;
authors.forename: Ellen
authors.initials: E
authors.lastname: Kantor
authors.forename: Hülya
authors.initials: H
authors.lastname: Bayır
authors.forename: Dianxu
authors.initials: D
authors.lastname: Ren
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Provencio
authors.forename: Laura
authors.initials: L
authors.lastname: Watkins
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Crago
authors.forename: Michael B
authors.initials: MB
authors.lastname: Horowitz
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: Yvette P
authors.initials: YP
authors.lastname: Conley
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Alexander
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D003627:Data Interpretation, Statistical; D005260:Female; D005838:Genotype; D015600:Glasgow Coma Scale; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012959:Socioeconomic Factors; D013345:Subarachnoid Hemorrhage / Q000235:genetics* / Q000401:mortality / Q000601:surgery*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006242:Haptoglobins; D004247:DNA