Article

Mortality predictions following traumatic brain injury (TBI), and our
understanding of TBI pathology, may be improved by including genetic risk in
addition to traditional prognostic variables. One promising target is the gene
coding for brain-derived neurotrophic factor (BDNF), a ubiquitous neurotrophin
important for neuronal survival and neurogenesis. OBJECTIVE:
We 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. METHODS: This study examined BDNF functional single
nucleotide polymorphisms rs6265 (val66met) and rs7124442 (T>C) in relation to
mortality in a prospective, longitudinal cohort with severe TBI. We examined 315
individuals receiving care for a closed head injury within the University of
Pittsburgh Medical Center, aged 16 to 74 years. Mortality was examined acutely
(0-7 days postinjury) and postacutely (8-365 days postinjury). 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: 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. CONCLUSIONS: 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.
CI - (c) The Author(s) 2014.

Langue : ANGLAIS