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J Neurotrauma. 2019 Mar 8. doi: 10.1089/neu.2018.6052. [Epub ahead of print]

The Apolipoprotein E4 polymorphism and outcomes from traumatic brain injury: a living systematic review and meta-analysis.

Author information

1
University of Cambridge, Division of Anaesthesia , Addenbrooke's Hospital , Hills Road , Cambridge, United Kingdom of Great Britain and Northern Ireland , CB2 0QQ ; charles.mcfadyen@nhs.net.
2
University of Cambridge, Division of Anaesthesia, Cambridge, United Kingdom of Great Britain and Northern Ireland.
3
University of Manitoba College of Medicine, 12359, Section of Neurosurgery, Department of Surgery, Winnipeg, Manitoba, Canada.
4
University of Manitoba, Clinician Investigator Program, Winnipeg, Manitoba, Canada ; faz22@cam.ac.uk.
5
University of Cambridge, Division of Anaesthesia , Addenbrookes Hospital , Cambridge, Cambs, United Kingdom of Great Britain and Northern Ireland , cb2 0qq ; vfjn2@cam.ac.uk.
6
Australasian Cochrane Centre, 67424, Monash University, Melbourne, Victoria, Australia ; Anneliese.synnot@monash.edu.
7
Erasmus MC, Public Health, Rotterdam, Netherlands.
8
Leids Universitair Medisch Centrum, 4501, Department of Biomedical Data Sciences, Leiden, Zuid-Holland, Netherlands ; e.steyerberg@erasmusmc.nl.
9
Nanyang Technological University, 54761, NTU Institute for Health Technologies and the Lee Kong Chian School of Medicine, Singapore, Singapore ; russell.gruen@anu.edu.au.
10
Harvard Medical School, Stroke Service, Department of Neurology, Massachusetts General Hospital and Center for Human Genetic Research, Massachusetts General Hopsital, Boston, Massachusetts, United States ; jrosand@partners.org.
11
Harvard Medical School, 1811, Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States ; aarno.palotie@fimm.fi.
12
University Hospital Antwerp, Emeritus Professor of Neurosurgery, Edegem, Belgium ; Andrew.Maas@uza.be.
13
University of Cambridge, Head, Division of Anaesthesia, Cambridge, Cambs, United Kingdom of Great Britain and Northern Ireland ; dkm13@cam.ac.uk.

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 grey 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 GRADE 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 favourable outcome following TBI in those not possessing an ApoE ε4 allele as compared to ε4 carriers and homozygotes (OR 1.39, 95% CI 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 ε4 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.

KEYWORDS:

GENETIC FACTORS; OUTCOME MEASURES; TRAUMATIC BRAIN INJURY

PMID:
30848161
DOI:
10.1089/neu.2018.6052

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