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Genetic Influences on Patient-Oriented Outcomes in Traumatic Brain Injury: A Living Systematic Review of Non-Apolipoprotein E Single-Nucleotide Polymorphisms.

Accepted version
Peer-reviewed

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Authors

Zeiler, Frederick A 
McFadyen, Charles 
Newcombe, Virginia FJ 
Synnot, Anneliese 
Donoghue, Emma L 

Abstract

There is a growing literature on the impact of genetic variation on outcome in traumatic brain injury (TBI). Whereas a substantial proportion of these publications have focused on the apolipoprotein E (APOE) gene, several have explored the influence of other polymorphisms. We undertook a systematic review of the impact of single-nucleotide polymorphisms (SNPs) in non-apolipoprotein E (non-APOE) genes associated with patient outcomes in adult TBI). We searched EMBASE, MEDLINE, CINAHL, and gray literature from inception to the beginning of August 2017 for studies of genetic variance in relation to patient outcomes in adult TBI. Sixty-eight articles were deemed eligible for inclusion into the systematic review. The SNPs described were in the following categories: neurotransmitter (NT) in 23, cytokine in nine, brain-derived neurotrophic factor (BDNF) in 12, mitochondrial genes in three, and miscellaneous SNPs in 21. All studies were based on small patient cohorts and suffered from potential bias. A range of SNPs associated with genes coding for monoamine NTs, BDNF, cytokines, and mitochondrial proteins have been reported to be associated with variation in global, neuropsychiatric, and behavioral outcomes. An analysis of the tissue, cellular, and subcellular location of the genes that harbored the SNPs studied showed that they could be clustered into blood-brain barrier associated, neuroprotective/regulatory, and neuropsychiatric/degenerative groups. Several small studies report that various NT, cytokine, and BDNF-related SNPs are associated with variations in global outcome at 6-12 months post-TBI. The association of these SNPs with neuropsychiatric and behavioral outcomes is less clear. A definitive assessment of role and effect size of genetic variation in these genes on outcome remains uncertain, but could be clarified by an adequately powered genome-wide association study with appropriate recording of outcomes.

Description

Keywords

genetics, living systematic review, outcome, prognosis, traumatic brain injury, Apolipoproteins E, Brain Injuries, Traumatic, Brain-Derived Neurotrophic Factor, Cytokines, Genetic Association Studies, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Treatment Outcome

Journal Title

J Neurotrauma

Conference Name

Journal ISSN

0897-7151
1557-9042

Volume Title

38

Publisher

Mary Ann Liebert Inc
Sponsorship
Academy of Medical Sciences (unknown)
European Commission (602150)
Authors received funding from the European Union FP 7th Framework program under grant agreement No 602150 (CENTER-TBI).