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Genetic Influences On Outcome Following Acute Neurological Insults

Ryan J. Waters, J. Nicoll
Published 2005 · Medicine

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Purpose of reviewTo examine the evidence for a genetic influence on clinical outcome after a variety of acute neurologic events. Recent findingsClinical 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. SummaryThere 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.
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A study examining the association of apolipoprotein E genotype and long-term outcome measures
This paper expands the association of apolipoprotein E and outcome after TBI in a Chinese patient population
The first paper to consider APOE promoter polymorphisms as a possible influence on outcome
A study of a unique black African cohort and the influence of e4 on outcome after TBI
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An interesting study that measured serial arterial and jugular IL-6 levels and attempted to correlate these, as well as IL-6 genotypes, with outcome
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An interesting multi-center study of multiple SNPs, including one recently identified
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