Genetic Influences on Patient-Oriented Outcomes in Traumatic Brain Injury: A Living Systematic Review of Non-Apolipoprotein E Single-Nucleotide Polymorphisms.
Donoghue, Emma L
Steyerberg, Ewout W
Gruen, Russel L
McAllister, Thomas W
Maas, Andrew IR
Journal of neurotrauma
Mary Ann Liebert
MetadataShow full item record
Zeiler, F., McFadyen, C., Newcombe, V., Synnot, A., Donoghue, E. L., Ripatti, S., Steyerberg, E. W., et al. (2021). Genetic Influences on Patient-Oriented Outcomes in Traumatic Brain Injury: A Living Systematic Review of Non-Apolipoprotein E Single-Nucleotide Polymorphisms.. Journal of neurotrauma, 38 (8), 1107-1123. https://doi.org/10.1089/neu.2017.5583
There is a growing literature on the impact of genetic variation on outcome in traumatic brain injury (TBI). While 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 (SNP) in non-apolipoprotein E (non-APOE) genes associated with patient outcomes in adult traumatic brain injury (TBI). We searched EMBASE, MEDLINE, CINAHL and grey 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 9, brain derived neurotrophic factor (BDNF) in 12, mitochondrial genes in 3, 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 behavioural outcomes. An analysis of the tissue, cellular, and subcellular location of the genes that harboured 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 to 12 months post-TBI. The association of these SNPs with neuropsychiatric and behavioural 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.
Authors received funding from the European Union FP 7th Framework program under grant agreement No 602150 (CENTER-TBI).
Academy of Medical Sciences (unknown)
EC FP7 CP (602150)
External DOI: https://doi.org/10.1089/neu.2017.5583
This record's URL: https://www.repository.cam.ac.uk/handle/1810/278523