Abstract 3242: Brain-derived Neurotrophic Factor Val66Met Polymorphism is Associated with Worsening of Functional Outcome in Patients Undergoing Resection of Unruptured Brain Arteriovenous Malformations

Abstract

Background: Brain-derived neurotrophic factor (BDNF) is a neuroprotective agent rapidly elevated after brain injury and necessary for recovery. A functional polymorphism in the BDNF gene, Val66Met, is associated with decreased BDNF secretion, and associated with worse outcome and slower recovery in Met carriers. Thus, we hypothesized that BDNF genotype might be associated with functional outcome following brain arteriovenous malformation (BAVM) resection. Because the effect of resection on a brain previously injured by hemorrhage might be less, we separately considered patients who presented with and without a hemorrhage. Methods: Val66Met was genotyped in 258 patients undergoing BAVM resection at UCSF with outcome data. Subjects were stratified into two groups based on hemorrhagic state at initial presentation (hemorrhage n=120, non-hemorrhage n=138). Poor outcome was defined as worsening on the modified Rankin scale (mRS) between pre-treatment (but post-hemorrhage) and last post-treatment follow-up visit. Univariate and multivariate logistic regression analysis, adjusting for age, gender, white race/ethnicity, AVM size, and length of follow up was performed. Sensitivity analysis was conducted by repeating the analysis in 158 Caucasian patients. Additionally, 4 BDNF tag SNPs (rs7124442, rs10767665, rs11030102, and rs12288512) were genotyped in 138 Caucasian patients. Results: Carriers of the Met allele of Val66Met had poor outcome after surgery among non-hemorrhaged patients (OR=2.4, CI=1.1-5.2, p=0.03), but there was not a statistically significant result among hemorrhaged patients (OR=0.7, 95% CI=0.2-2.0, p=0.5). The association remained after multivariable adjustment (non-hemorrhaged: OR=2.8, 95% CI=1.2-6.5, p=0.01; hemorrhaged: OR=1.0, 95% CI=0.3-3.2, p=1.0). In the Caucasian subgroup, similar results were observed; among non-hemorrhaged patients, Met carriers had poor outcome in univariate (OR=2.1, CI=0.8-5.6, p=0.1) and multivariate analysis (OR=3.0, CI=1.1-8.8, p=0.04). No association was established among hemorrhaged patients. No association was observed with other BDNF tag SNPs. Conclusions: The Val66Met polymorphism in BDNF is associated with poor surgical outcome in unruptured BAVM patients. These results warrant further investigation in larger studies but suggest that BNDF could play an important role in evaluating surgical risk.