Variation in the BDNF gene interacts with age to predict mortality in a prospective, longitudinal cohort with severe TBI

Short Title:
Variation in the BDNF gene interacts with age to predict mortality in a prospective, longitudinal cohort with severe TBI
Model System:
TBI
Reference Type:
Journal Article
Accession No.:
J70724
Journal:
NEUROREHABILITATION AND NEURAL REPAIR
Year, Volume, Issue, Page(s):
2014, vol. 1, issue , pp n/a
Publication Website:
Abstract:
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.
Author(s):
Failla MD, Kumar RG, Peitzman A, Conley YP, Ferrell RE, Wagner AK.
Author Address(es):
Participating Centers:

Some items may be available for document delivery from the National Rehabilitation Information Center. Make a note of the title and any accession number and contact NARIC at 800-346-2742 to request a copy. There is a charge for document delivery from the NARIC collection.