Brain-derived neurotrophic factor Val66Met polymorphism predicts worse functional outcome after surgery in patients with unruptured brain arteriovenous malformation

Stroke. 2012 Aug;43(8):2255-7. doi: 10.1161/STROKEAHA.112.663096. Epub 2012 Jul 5.

Abstract

Background and purpose: The Val66Met polymorphism of brain-derived neurotrophic factor is associated with decreased brain-derived neurotrophic factor secretion and poor outcome after acute neurological injury. We hypothesized that the Met allele is associated with worsening of functional outcome after brain arteriovenous malformation resection.

Methods: Three hundred forty-one surgically treated patients with brain arteriovenous malformation with outcome data were genotyped for Val66Met. Outcome was change in modified Rankin Scale preoperatively versus postoperatively, dichotomized into poor (change >0) or good outcome (change ≤0). Likelihood ratio tests for interactions and logistic regression analysis were performed.

Results: A significant interaction (P=0.03) of Val66Met genotype and hemorrhagic presentation existed; thus, ruptured and unruptured patients were considered separately. The Met allele was associated with increased risk of poor outcome among patients presenting unruptured (OR, 2.15; 95% CI, 1.02-4.55; P=0.045) but not ruptured (OR, 0.54; 95% CI, 0.19-1.53; P=0.25), adjusting for covariates.

Conclusions: The Val66Met polymorphism is associated with worsened surgical outcome in patients with unruptured brain arteriovenous malformation, a group that currently has no good risk predictors. Further studies replicating these findings are needed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Amino Acid Substitution
  • Analysis of Variance
  • Brain-Derived Neurotrophic Factor / genetics*
  • Female
  • Genotype
  • Heterozygote
  • Humans
  • Intracranial Arteriovenous Malformations / genetics*
  • Intracranial Arteriovenous Malformations / surgery*
  • Logistic Models
  • Male
  • Methionine / genetics
  • Middle Aged
  • Neurosurgical Procedures*
  • Polymorphism, Genetic / genetics
  • Predictive Value of Tests
  • Rupture, Spontaneous / pathology
  • Treatment Outcome
  • Valine / genetics

Substances

  • Brain-Derived Neurotrophic Factor
  • Methionine
  • Valine