Short Title:Neurorehabilitation and Neural Repair
Year, Volume, Issue, Page(s):15, 29, 3, 234-246
Study examined brain-derived neurotrophic factor (BDNF) functional single nucleotide polymorphisms rs6265 and rs7124442 in relation to mortality in 315 individuals, aged 16 to 74 years, receiving care for severe traumatic brain injury (TBI). It was hypothesized the addition of BDNF genetic variation would improve mortality prediction models and that BDNF Met-carriers (rs6265) and C-carriers (rs7124442) would have the highest mortality rates post-TBI. Mortality was examined acutely (0 to 7 days after injury) and postacutely (8 to 365 days after injury). A gene risk score (GRS) was developed to examine both BDNF loci. Cox proportional hazards models were used to calculate hazard ratios for survivability post-TBI while controlling for covariates. Results showed that BDNF GRS was significantly associated with acute mortality, regardless of age. Interestingly, subjects in the hypothesized no-risk allele group had the lowest survival probability. Postacutely, BDNF-GRS interacted with age such that younger participants in the no-risk group had the highest survival probability, while older participants in the hypothesized no-risk group had the lowest probability of survival. These data suggest complex relationships between BDNF and TBI mortality that interact with age to influence survival predictions beyond clinical variables alone. Evidence supporting dynamic, temporal balances of pro-survival/pro-apoptotic target receptors may explain injury and age-related gene associations.