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Genetic influences on outcome following acute neurological insults

Waters, Ryan J; Nicoll, James A. R

Current Opinion in Critical Care: April 2005 - Volume 11 - Issue 2 - p 105-110
doi: 10.1097/01.ccx.0000155354.78617.91

Purpose of review To examine the evidence for a genetic influence on clinical outcome after a variety of acute neurologic events.

Recent findings Clinical outcome after brain injury is variable and cannot easily be predicted. It has been proposed that genetic polymorphisms may have an important role in determining outcome from a number of conditions, including acute neurologic events. Apolipoprotein E, an important mediator of cholesterol and lipid transport in the brain, is coded by a polymorphic gene (APOE). The APOE ε4 allele has been associated with unfavorable outcome after traumatic brain injury (TBI), hemorrhagic stroke and subarachnoid hemorrhage (SAH). Genes involved in other pathophysiological processes, such as cytokine genes in neuroinflammation, are now being implicated. For example interleukin-6 (IL-6) promoter polymorphisms are a risk factor for poor outcome after ischemic stroke, and may have an effect after traumatic brain injury. The emerging importance of a number of other gene polymorphisms is outlined in the review.

Summary There is evidence demonstrating the ε4 allele of APOE predisposes to poor outcome after TBI, hemorrhagic stroke and SAH, but not ischemic stroke. The reason for this difference is unclear but it suggests there may be differences in the key mechanisms underlying the response to different types of insult. The role of other gene polymorphisms is being increasingly explored but there is still a need for larger prospective studies looking at larger panels of gene polymorphisms.

Division of Clinical Neuroscience, University of Southampton, UK

Correspondence to R.J. Waters, MD, Division of Clinical Neuroscience, Room 6207, Biomedical Science Building, Bassett Crescent East, University of Southampton, SO16 7PX UK

Tel: +44 023 80 597804; fax: +44 023 80 597809; e-mail:

© 2005 Lippincott Williams & Wilkins, Inc.