Apolipoprotein E-ε4 genotype predicts a poor outcome in survivors of traumatic brain injury

Objective: To determine the ability of apolipoprotein E (APOE) genotypes to predict days of unconsciousness and a suboptimal functional outcome in traumatic brain injury (TBI) survivors. Background: TBI is known to be associated with neuropsychological deficits and functional disability. Recent evidence indicates that APOE plays a pivotal role in CNS response to injury. Methods: In this prospective study the authors determined the APOE genotypes and tested their ability to predict days of unconsciousness and functional outcome after at least 6 months in 69 survivors of TBI. A good functional outcome was defined as no dysarthria, behavioral abnormalities, or dysphasia; no severe cognitive abnormalities; and the ability to live independently. Results: The odds ratio of more than 7 days of unconsciousness was 5.69 in those with the APOE-epsilon 4 allele compared with those without the epsilon 4 allele (95% CI, 1.69 to 20.0; p = 0.001). Only 1 of 27 subjects (3.7%) with the epsilon 4 allele had a good functional outcome compared with 13 of 42 (31.0%) of those without the epsilon 4 allele (p = 0.006). The OR of a suboptimal outcome (fair or unfavorable) was 13.93 for those with the epsilon 4 allele compared with those without the allele after controlling for age and time of unconsciousness (95% CI, 1.45 to 133.97; p = 0.02). Conclusion: The results demonstrate a strong association between the APOE-epsilon 4 allele and a poor clinical outcome, implying genetic susceptibility to the effect of brain injury. Additional studies of TBI patients are warranted to confirm their findings.