PMID- 25063686
OWN - NLM
STAT- MEDLINE
DCOM- 20160106
LR  - 20211021
IS  - 1552-6844 (Electronic)
IS  - 1545-9683 (Print)
IS  - 1545-9683 (Linking)
VI  - 29
IP  - 3
DP  - 2015 Mar-Apr
TI  - Variation in the BDNF gene interacts with age to predict mortality in a 
      prospective, longitudinal cohort with severe TBI.
PG  - 234-46
LID - 10.1177/1545968314542617 [doi]
AB  - BACKGROUND: 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.
FAU - Failla, Michelle D
AU  - Failla MD
AD  - Department of Physical Medicine & Rehabilitation, University of Pittsburgh, 
      School of Medicine, Pittsburgh PA Center for Neuroscience, University of 
      Pittsburgh, Pittsburgh, PA.
FAU - Kumar, Raj G
AU  - Kumar RG
AD  - Department of Physical Medicine & Rehabilitation, University of Pittsburgh, 
      School of Medicine, Pittsburgh PA.
FAU - Peitzman, Andrew B
AU  - Peitzman AB
AD  - Department of Surgery, University of Pittsburgh, School of Medicine, Pittsburgh 
      PA.
FAU - Conley, Yvette P
AU  - Conley YP
AD  - Department of Health Promotion & Development, University of Pittsburgh, School of 
      Nursing, Pittsburgh, PA.
FAU - Ferrell, Robert E
AU  - Ferrell RE
AD  - Department of Human Genetics, University of Pittsburgh, School of Public Health, 
      Pittsburgh, PA.
FAU - Wagner, Amy K
AU  - Wagner AK
AD  - Department of Physical Medicine & Rehabilitation, University of Pittsburgh, 
      School of Medicine, Pittsburgh PA Center for Neuroscience, University of 
      Pittsburgh, Pittsburgh, PA Safar Center for Resuscitation Research, University 
      Pittsburgh, Pittsburgh, PA wagnerak@upmc.edu.
LA  - eng
GR  - UL1 TR000005/TR/NCATS NIH HHS/United States
GR  - R01NR008424/NR/NINR NIH HHS/United States
GR  - R01NR013342/NR/NINR NIH HHS/United States
GR  - R01HD048162/HD/NICHD NIH HHS/United States
GR  - R01 NR008424/NR/NINR NIH HHS/United States
GR  - R01 NR013342/NR/NINR NIH HHS/United States
GR  - R01 HD048162/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20140724
PL  - United States
TA  - Neurorehabil Neural Repair
JT  - Neurorehabilitation and neural repair
JID - 100892086
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 7171WSG8A2 (BDNF protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Brain Injuries/*genetics/*mortality
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Longitudinal Studies
MH  - Male
MH  - Middle Aged
MH  - Mortality
MH  - Polymorphism, Single Nucleotide
MH  - Prognosis
MH  - Prospective Studies
MH  - ROC Curve
MH  - Risk Factors
MH  - Young Adult
PMC - PMC4305354
MID - NIHMS606289
OTO - NOTNLM
OT  - BDNF
OT  - TrkB
OT  - age
OT  - brain injury
OT  - genetic association study
OT  - mortality
EDAT- 2014/07/27 06:00
MHDA- 2016/01/07 06:00
PMCR- 2016/03/01
CRDT- 2014/07/27 06:00
PHST- 2014/07/27 06:00 [entrez]
PHST- 2014/07/27 06:00 [pubmed]
PHST- 2016/01/07 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - 1545968314542617 [pii]
AID - 10.1177/1545968314542617 [doi]
PST - ppublish
SO  - Neurorehabil Neural Repair. 2015 Mar-Apr;29(3):234-46. doi: 
      10.1177/1545968314542617. Epub 2014 Jul 24.