Brain Derived Neurotrophic Factor (BDNF) Val66Met Single Nucleotide Polymorphism (rs6265) is Associated With Decreased Functional Outcome After Traumatic Brain Injury: A Multicenter Cohort Study

Abstract

Abstract INTRODUCTION Brain-derived neurotrophic factor (BDNF) is a common neurotrophin important to neuronal survival and plasticity. We aim to elucidate the associations between the BDNF single nucleotide polymorphism (SNP) Val66Met (rs6265) and 3-mo outcome after traumatic brain injury (TBI). METHODS TBI subjects from the prospective, multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study conducted across 3 US Level I trauma centers were eligible. All subjects presented to emergency department < 24 h of injury and received a brain computed tomography (CT) scan as part of clinical care. Patients aged = 18-yr with Marshall CT Score 1 to 3 were included. Associations between BNDF rs6265 (Val/Val vs Met-carriers), demographic/injury factors, and 3-mo Glasgow Outcome Scale-Extended (GOSE) were analyzed. Multivariable regression was performed for BDNF and outcomes, controlling for age, sex, education, GCS, CT, and polytrauma. Odds ratios (OR) and 95% CIs are shown. Significance was assessed at P < .05. RESULTS A total of 180 TBI subjects were aged 45.5 ± 18.3-yr, 68.5% male, and 81% Caucasian. Subjects were GCS 13 to 15, with 40% CT-positive and 16% polytrauma, which did not differ by BDNF. In all 64% were Val/Val (vs 36% Met-carriers). At 3-mo, functional impairment (GOSE < 7) was present in 33% (Val/Val: 26%, Met-carrier: 46%, P = .006), and 28% were unable to resume baseline work capacity (Val/Val: 21%, Met-carrier: 40%, P = .006). These results were conserved when stratified by CT. In CT-negative subjects, Met-carriers were at risk for functional impairment (univariate-OR = 3.0, 95% CI [1.1-7.4]) and inability to return to baseline work (RTBW; univariate-OR = 3.0 [1.2-7.4]). For CT-positive subjects, results were similar for functional impairment (univariate-OR = 2.4 [0.9-6.3]) and inability to RTBW (univariate-OR = 2.4 [0.9-6.3]). On multivariable analysis, BDNF Met-carriers were at elevated risk for functional impairment (OR = 2.5 [1.2-5.0]) and inability to RTBW (OR = 2.6 [1.2-5.4]). CONCLUSION BDNF rs6265 SNP may associate with TBI outcomes, with Met-carriers at increased risk of 3-mo functional impairment and inability to RTBW. Future confirmatory studies are needed.