| BCL2 genotypes: functional and neurobehavioral outcomes after severe traumatic brain injury. | |
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MedLine Citation:
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PMID: 20504155 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Traumatic brain injury (TBI) triggers a cascade of apoptotic-related events that include BCL2 expression, a pro-survival protein in the apoptosis pathway. The purpose of this study was to use tagging single nucleotide polymorphism (tSNP) genotypes to screen the BCL2 gene to determine if genetic variability in the BCL2 gene influences outcomes in 205 patients with severe TBI. Outcomes (Glasgow Outcome Scale [GOS], Disability Rating Scale [DRS], mortality, and Neurobehavioral Rating Scale-Revised [NRS-R]) were analyzed at 3, 6, 12, and 24 months. Multivariate analysis demonstrates that there were four tSNPs of significant interest: rs17759659, rs1801018, rs7236090, and rs949037. Presence of the variant allele for rs17759659 was associated with poorer outcomes (GOS p = 0.001; DRS p = 0.002), higher mortality (p = 0.02; OR = 4.23; CI 1.31,13.61), and worse NRS-R scores (p = 0.05). Presence of the variant allele for rs1801018 was associated with poorer outcomes (GOS p = 0.02; DRS p = 0.009), and mortality (p = 0.03; OR = 3.86; CI 1.18,12.59). Being homozygous for the wild-type allele for rs7236090 was associated with favorable outcomes on the NRS-R (p = 0.007), while homozygosity for the variant genotype was associated with favorable outcomes on the GOS (p = 0.007) and DRS (p = 0.006). The homozygous variant for rs949037 was associated with favorable outcomes (GOS p = 0.04; DRS p = 0.03), and the homozygous wild-type was associated with increased mortality at 3 months (p = 0.005; OR = 3.67; CI 1.08,12.49). The only finding that stood up to Bonferroni correction was rs17759659 for GOS. These data support the possibility that genetic variability for pro-survival proteins, particularly genetic variation in the BCL2 gene, impacts outcomes after severe TBI. |
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Authors:
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Nicole Zangrilli Hoh; Amy K Wagner; Sheila A Alexander; Robert B Clark; Sue R Beers; David O Okonkwo; Dianxu Ren; Yvette P Conley |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of neurotrauma Volume: 27 ISSN: 1557-9042 ISO Abbreviation: J. Neurotrauma Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-17 Completed Date: 2010-12-02 Revised Date: 2013-05-01 |
Medline Journal Info:
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Nlm Unique ID: 8811626 Medline TA: J Neurotrauma Country: United States |
Other Details:
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Languages: eng Pagination: 1413-27 Citation Subset: IM |
Affiliation:
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University of Pittsburgh School of Nursing, Department of Health Promotion and Development, Pittsburgh, Pennsylvania 15261, USA. nmzst1@pitt.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Behavior / physiology* Brain Injuries / genetics*, pathology*, psychology Cognition / physiology Data Interpretation, Statistical Disability Evaluation Female Genes, bcl-2 / genetics* Genotype Glasgow Outcome Scale Haplotypes Humans Longitudinal Studies Male Middle Aged Neuropsychological Tests Recovery of Function Reverse Transcriptase Polymerase Chain Reaction Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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5P50NS30318/NS/NINDS NIH HHS; NR008424/NR/NINR NIH HHS; R01 NR008424/NR/NINR NIH HHS; R01NR04801/NR/NINR NIH HHS; R49/CCR 323155-03//PHS HHS; T32 NR009759/NR/NINR NIH HHS; T32 NR009759/NR/NINR NIH HHS |
| Comments/Corrections | |
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