Nathoo, N., Chetry, R., van Dellen, J. R., Connolly, C. & Naidoo, R. Apolipoprotein E polymorphism and outcome after closed traumatic brain injury: influence of ethnic and regional differences. J. Neurosurg. 98, 302-306
The presence of the apolipoprotein E-epsilon4 (APOE-epsilon4) allele is reported to be associated with poor outcome after traumatic brain injury (TBI). This study was performed to determine if the presence of the APOE-epsilon4 allele influenced outcome in a cohort of black patients with TBI who had homogeneous neuropathological findings.
Venous blood was collected at the time of admission to determine the APOE genotype in black Zulu-speaking patients who presented with traumatic cerebral contusions. The frequency of the APOE-epsilon4 allele's appearance was correlated with outcome at a minimum of 6 months of follow up. Univariate and multivariate analyses were performed to determine independent risk factors and to control for confounding factors. In 110 black Zulu-speaking patients with traumatic cerebral contusions, genotypes for APOE were analyzed. Eleven of 45 (24.4%) with the APOE-epsilon4 allele experienced a poor outcome, compared with 10 (15.4%) of 65 without this allele (p = 0.34). Both patients with homozygous APOE-epsilon4 alleles experienced a good outcome (Glasgow Outcome Score 5). Univariate and multivariate analysis revealed no significant relationship in patients with the APOE-epsilon4 allele with regard to age, admission Glasgow Comas Scale score, contusion volume, type of neurosurgical management, and outcome. The risk of a poor outcome was, however, greater in patients with the APOE-epsilon4 allele (relative risk 1.59; 95% confidence interval 0.74-3.42).
The authors recorded no relationship between APOE-epsilon4 allele status and outcome after TBI in black patients. Given the high regional susceptibility to the APOE gene, further studies, possibly even community-based investigations and studies conducted in other geographic areas, are probably warranted.
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"A prospective study of 106 patients with moderate to severe brain injury found that patients carrying the ε4 allele had a 2.4 relative risk of seizures . Studies have found that carrying the ε4 allele is associated with worst outcome in some studies of patients with TBI    , but not all studies   . "
[Show abstract][Hide abstract] ABSTRACT: The relationship of genetic predisposition to reduced iron capacity and apolipoprotein E (APOE) to posttraumatic seizures (PTSs) and neuropsychological outcomes was investigated in patients with traumatic brain injuries from a prior valproate clinical study. Haptoglobin concentration/phenotype and APOE genotype were determined in 25 patients with PTSs and 26 control (no PTSs) subjects approximately 10 years after traumatic brain injury. Haptoglobin phenotype was also determined in previously collected frozen samples for 25 additional patients with PTSs and 32 no-PTS subjects. There was no relationship between haptoglobin phenotype or APOE genotype and occurrence of PTSs. APOE genotype was not related to neuropsychological outcome; however, when adjustments were made for differences in educational levels, APOE epsilon4 subjects did worse, especially on tests of verbal intellectual and verbal memory skills. In contrast to our hypothesis, those with haptoglobin 1-1 (high-affinity binder of hemoglobin) scored somewhat worse on Verbal IQ and Tapping D at 1 and 12 months after injury.
"Subsequent studies have indicated reduced prospects for recovery in APOE «4 carriers during rehabilitation after head injury (Friedman et al., 1999; Lichtman et al., 2000; Crawford et al., 2002; Liberman et al., 2002; Chiang et al., 2003). Some studies have shown little or no evidence of an association between APOE genotype and outcome in relatively mild injuries (Sundstrom et al., 2004; Chamelian et al., 2004) or in a South African Black population in whom APOE «4 is relatively common (Nathoo et al., 2003). All of the studies referred to above differ in terms of patient selection, severity of injury and method of outcome assessment, and all suffer from small sample size with which to reliably detect genetic associations. "
[Show abstract][Hide abstract] ABSTRACT: Previous preliminary studies have suggested that possession of the APOE epsilon4 allele is associated with a poor outcome after head injury. This study was designed to confirm and extend those observations in a larger study with examination of additional variables. We prospectively identified admissions to a Neurosurgical Unit for head injury, collected demographic and clinical data, determined APOE genotypes and obtained follow-up information at 6 months. A total of 1094 subjects were enrolled (age range: 0-93 years, mean 37 years). Outcome was assessed using the Glasgow Outcome Scale. There was no overall association between APOE genotype and outcome, with 36% of APOE epsilon4 carriers having an unfavourable outcome compared with 33% of non-carriers of APOE epsilon4. However, there was evidence of an interaction between age and APOE genotype on outcome (P = 0.007) such that possession of APOE epsilon4 reduced the prospect of a favourable outcome in children and young adults. The influence of APOE genotype in younger patients after head injury can be expressed as, at age <15 years, carriage of APOE epsilon4 being equivalent to ageing by 25 years. This finding is consistent with experimental data suggesting that the effect of APOE genotype on outcome after head injury may be expressed through the processes of repair and recovery.
"predominantly Caucasian population that attends our hospital and from which our study sample was derived. A unique study (Nathoo et al., 2003) that focused exclusively on the Zulu tribe in South Africa once again found that, despite the high prevalence of the APOE-e4 allele in 110 subjects, outcome following mostly mild to moderate TBI was not linked to APOE polymorphism. Language barriers may have precluded a detailed cognitive assessment in determining recovery, which was based exclusively on the GOS. "
[Show abstract][Hide abstract] ABSTRACT: The possession of at least one APOE-epsilon4 allele may be linked to poor outcome in patients with predominantly severe traumatic brain injury (TBI). In mild TBI, which accounts for approximately 85% of all cases, the role of the APOE-epsilon4 allele is less clear. Studies completed to date have relied on brief cognitive assessments or coarse measures of global functioning, thereby limiting their conclusions. Our study investigated the influence of the APOE-epsilon4 allele in a prospective sample of 90 adults with mild to moderate TBI in whom neuropsychiatric outcome 6 months after injury was assessed as follows: (i) a detailed neuropsychological battery; (ii) an index of emotional distress (General Health Questionnaire); (iii) a diagnosis of major depression (Structured Clinical Interview for DSM-IV); (iv) a measure of global functioning (Glasgow Outcome Scale); (v) an index of psychosocial outcome (Rivermead Head Injury Follow-up Questionnaire); and (vi) symptoms of persistent post-concussion disorder (Rivermead Post-Concussion Symptoms Questionnaire). No association was found between the presence of the APOE-epsilon4 allele and poor outcome across all measures. Given the homogeneous nature of our sample (mild to moderate injury severity), the uniform follow-up period (6 months) and the comprehensive markers of recovery used, our data suggest that the APOE-epsilon4 allele does not adversely impact outcome in this group of TBI patients.