title: Systematic Review of Genetic Risk Factors for Sustaining a Mild Traumatic Brain Injury.
abstract: This systematic review examined the association between genetics and risk for sustaining a traumatic brain injury. We retrieved articles published in English from 1980 to July 2016 obtained from the online databases PubMed, PsycINFO®, MEDLINE®, Embase, and Web of Science. In total 5903 articles were identified, 77 underwent full-text screening, and 6 were included in this review. Five studies examined the risk of concussion associated with apolipoprotein E alleles (APOE-ɛ2, ɛ3,ɛ4), and polymorphisms of the APOE promoter (rs405509), brain derived neurotrophic factor (BDNF, rs6265), and dopamine receptor D2 (DRD2, rs1800497) were each considered in two studies. Microtubule associated protein tau (TAU exon 6 polymorphisms His47Tyr [rs2258689] and Ser53Pro [rs10445337]), and neurofilament heavy (NEHF, rs165602) genotypic variants, were the focus of single studies. No study showed an increased risk associated solely with the presence of the APOE-ɛ4 allele, nor were there any significant findings for the NEFH, TAU, or DRD2 genotypic variants. Two studies examined the APOE promoter -219G/T polymorphism in athletes, and both found an association with concussion. Both BDNF studies also found a significant association with concussion incidence; United States soldiers with the Met/Met genotype were more likely to report a history of concussion prior to deployment and to sustain a concussion during deployment. We conclude that the APOE promoter -219G/T polymorphism and the BDNF Met/Met genotype might confer risk for sustaining a TBI. Based on research to date, the APOE-ɛ4 allele does not appear to influence risk. More research is needed to determine if these findings replicate.
authors.affiliation: 1 British Columbia Neuropsychiatry Program and Department of Psychiatry, University of British Columbia , Vancouver, British Columbia, Canada .
authors.forename: William J
authors.initials: WJ
authors.lastname: Panenka
authors.affiliation: 2 Hunter New England Local Health District Sports Concussion Program; & Centre for Stroke and Brain Injury, School of Medicine and Public Health, University of Newcastle , Callaghan, New South Wales, Australia .
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gardner
authors.affiliation: 3 Human Dimension Division (HDD), Headquarters Army Training and Doctrine Command (HQ TRADOC) , Fort Eustis, Virginia.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Dretsch
authors.affiliation: 4 Roskamp Institute , Sarasota, Florida.
authors.forename: Gogce C
authors.initials: GC
authors.lastname: Crynen
authors.affiliation: 4 Roskamp Institute , Sarasota, Florida.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Crawford
authors.affiliation: 5 Department of Physical Medicine and Rehabilitation, Harvard Medical School; Spaulding Rehabilitation Hospital; MassGeneral Hospital for Children Sports Concussion Program; and Home Base, A Red Sox Foundation and Massachusetts General Hospital Program , Boston, Massachusetts.|6 Defense and Veterans Brain Injury Center , Bethesda, Maryland.
authors.forename: Grant L
authors.initials: GL
authors.lastname: Iverson
mesh_terms: D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics; D001924:Brain Concussion / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics; D012307:Risk Factors
chemical_list: D001057:Apolipoproteins E; D019208:Brain-Derived Neurotrophic Factor; C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2; C579455:BDNF protein, human
keywords: apolipoprotein E; concussion; genotype; mild traumatic brain injury; risk