Genetic influences on outcome following traumatic brain injury.
Several genes have been implicated as influencing the outcome following traumatic brain injury (TBI). Currently the most extensively studied gene has been APOE. APOE can influence overall and rehabilitation outcome, coma recovery, risk of posttraumatic seizures, as well as cognitive and behavioral functions following TBI. Pathologically, APOE is associated with increased amyloid deposition, amyloid angiopathy, larger intracranial hematomas and more severe contusional injury. The proposed mechanism by which APOE affects the clinicopathological consequences of TBI is multifactorial and includes amyloid deposition, disruption of cytoskeletal stability, cholinergic dysfunction, oxidative stress, neuroprotection and central nervous system plasticity in response to injury. Other putative genes have been less extensively studied and require replication of the clinical findings. The COMT and DRD2 genes may influence dopamine dependent cognitive processes such as executive/frontal lobe functions. Inflammation which is a prominent component in the pathophysiological cascade initiated by TBI, is in part is mediated by the interleukin genes, while apoptosis that occurs as a consequence of TBI may be modulated by polymorphisms of the p53 gene. The ACE gene may affect TBI outcome via mechanisms of cerebral blood flow and/or autoregulation and the CACNA1A gene may exert an influence via the calcium channel and its effect on delayed cerebral edema. Although several potential genes that may influence outcome following TBI have been identified, future investigations are needed to validate these genetic studies and identify new genes that might influence outcome following TBI.
Jordan
Barry D
BD
Brain Injury Program, Burke Rehabilitation Hospital, 785 Mamaroneck Avenue, White Plains, NY 10605, USA. bjordan@burke.org
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001930:Brain Injuries / Q000235:genetics* / Q000628:therapy*; D015220:Calcium Channels / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007378:Interleukins / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D016896:Treatment Outcome; D020864:Calcium Channels, N-Type
D001057:Apolipoproteins E; D015220:Calcium Channels; D002394:Catechol O-Methyltransferase; D007378:Interleukins; D007703:Peptidyl-Dipeptidase A; D017448:Receptors, Dopamine D2; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type