Association of apolipoprotein E polymorphism with outcome after head injury

Background Variation in outcome after head injury is not fully explained by known prognostic features. Polymorphism of the apolipoprotein E gene (APOE) influences neuropathological findings in patients who die from head injuries. More people who die from head injuries than non-head-injured controls have deposits of amyloid beta-protein in the cerebral cortex, with amyloid beta-protein deposits present predominantly in patients with the APOE epsilon 4 allele. We report a prospective clinical study to test the hypothesis that patients with APOE epsilon 4 have a worse clinical outcome 6 months after head injury than those without APOE epsilon 4. Methods We studied a prospectively recruited series of patients admitted alter a head injury to a neurosurgical unit (n=93). Assessment of severity of the initial injury was by means of the Glasgow Coma Score (GCS). Outcome 6 months after injury was assessed by means of the Glasgow Outcome Scale. APOE genotypes were determined from blood samples by standard methods. Findings Detailed information on outcome was available for 89 patients. 17 (57%) of 30 patients with APOE epsilon 4 had an unfavourable outcome (dead, vegetative state, or severe disability) compared with 16 (27%) of the 59 patients without APOE epsilon 4 (p=0.006). The association remained significant when adjustment was made to control for age, GCS, and computed tomography scan findings (p=0.024). Interpretation Our findings show a significant genetic association of APOE polymorphism with outcome after head injury supporting the hypothesis of a genetically determined influence. Patients with APOE epsilon 4 are more than twice as likely as those without APOE epsilon 4 to have an unfavourable outcome 6 months after head injury. Further studies are under way to confirm and further evaluate this association.