The Met allele of the BDNF Val66Met polymorphism predicts poor outcome among survivors of aneurysmal subarachnoid hemorrhage.

Abstract

Brain-derived neurotrophic factor (BDNF) plays a role in neuronal survival, plasticity and neurogenesis. The BDNF gene contains a common Val66Met polymorphism; the Met allele is associated with lower depolarization-induced BDNF release and differences in memory functions and brain morphology. We hypothesized that the Met allele is associated with poor recovery from subarachnoid hemorrhage. A sample of 105 survivors was assessed at 3 months after subarachnoid hemorrhage using Glascow Outcome Scale. Poor outcome was defined as severe disability or worse. DNA samples were genotyped for the Val66Met polymorphism. Higher percentage of the Met carriers had a poor outcome (29%) as compared with the Val/Val group (10%; P=0.011). In multiple logistic regression, this association between the Met allele and poor outcome was independent of several other prognostic factors such as patient age, clinical condition, and radiological severity of the bleeding (odds ratio 8.40; 95% CI, 1.60 to 44.00; P=0.012). Genetically influenced variation in BDNF function plays a role in recovery from subarachnoid hemorrhage. These data indicate that augmentation of BDNF signaling may be beneficial to recovery from brain injury.