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

Document Type

Article

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.

Medical Subject Headings

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

Publication Date

7-10-2012

Publication Title

Stroke

E-ISSN

1524-4628

Volume

43

Issue

8

First Page

2255

Last Page

7

PubMed ID

22773554

Digital Object Identifier (DOI)

10.1161/STROKEAHA.112.663096

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