Apolipoprotein E4 Polymorphism and Outcomes from Traumatic Brain Injury : A Living Systematic Review and Meta-Analysis

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McFadyen , C A , Zeiler , F A , Newcombe , V , Synnot , A , Steyerberg , E , Gruen , R L , Rosand , J , Palotie , A , Maas , A I R & Menon , D K 2021 , ' Apolipoprotein E4 Polymorphism and Outcomes from Traumatic Brain Injury : A Living Systematic Review and Meta-Analysis ' , Journal of Neurotrauma , vol. 38 , no. 8 , pp. 1124–1136 . https://doi.org/10.1089/neu.2018.6052

Title: Apolipoprotein E4 Polymorphism and Outcomes from Traumatic Brain Injury : A Living Systematic Review and Meta-Analysis
Author: McFadyen, Charles A.; Zeiler, Frederick A.; Newcombe, Virginia; Synnot, Anneliese; Steyerberg, Ewout; Gruen, Russel L.; Rosand, Jonathan; Palotie, Aarno; Maas, Andrew I. R.; Menon, David K.
Contributor organization: Centre of Excellence in Complex Disease Genetics
Aarno Palotie / Principal Investigator
Institute for Molecular Medicine Finland
Genomics of Neurological and Neuropsychiatric Disorders
University of Helsinki
HUS Helsinki and Uusimaa Hospital District
Date: 2021-04-15
Language: eng
Number of pages: 15
Belongs to series: Journal of Neurotrauma
ISSN: 0897-7151
DOI: https://doi.org/10.1089/neu.2018.6052
URI: http://hdl.handle.net/10138/340773
Abstract: The mortality of traumatic brain injury (TBI) has been largely static despite advances in monitoring and imaging techniques. Substantial variance exists in outcome, not fully accounted for by baseline characteristics or injury severity, and genetic factors likely play a role in this variance. The aims of this systematic review were to examine the evidence for a link between the apolipoprotein E4 (APOE4) polymorphism and TBI outcomes and where possible, to quantify the effect size via meta-analysis. We searched EMBASE, MEDLINE, CINAHL, and gray literature in December 2017. We included studies of APOE genotype in relation to functional adult TBI outcomes. Methodological quality was assessed using the Quality in Prognostic Studies Risk of Bias Assessment Instrument and the prognostic studies adaptation of the Grading of Recommendations Assessment, Development and Evaluation tool. In addition, we contacted investigators and included an additional 160 patients whose data had not been made available for previous analyses, giving a total sample size of 2593 patients. Meta-analysis demonstrated higher odds of a favorable outcome following TBI in those not possessing an ApoE e4 allele compared with e4 carriers and homozygotes (odds ratio 1.39, 95% confidence interval 1.05 to 1.84; p = 0.02). The influence of APOE4 on neuropsychological functioning following TBI remained uncertain, with multiple conflicting studies. We conclude that the ApoE e4 allele confers a small risk of poor outcome following TBI, with analysis by TBI severity not possible based on the currently available published data. Further research into the long-term neuropsychological impact and risk of dementia is warranted.
Subject: genetics
living systematic reviews
traumatic brain injury
3121 General medicine, internal medicine and other clinical medicine
3112 Neurosciences
3124 Neurology and psychiatry
Peer reviewed: Yes
Rights: cc_by_nc
Usage restriction: openAccess
Self-archived version: publishedVersion

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