Association of apolipoprotein E polymorphism with outcome after head injury

Abstract

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 epsilon4 allele. We report a prospective clinical study to test the hypothesis that patients with APOE epsilon4 have a worse clinical outcome 6 months after head injury than those without APOE epsilon4. We studied a prospectively recruited series of patients admitted after 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. Detailed information on outcome was available for 89 patients. 17 (57%) of 30 patients with APOE epsilon4 had an unfavourable outcome (dead, vegetative state, or severe disability) compared with 16 (27%) of the 59 patients without APOE epsilon4 (p=0.006). The association remained significant when adjustment was made to control for age, GCS, and computed tomography scan findings (p=0.024). 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 epsilon4 are more than twice as likely as those without APOE epsilon4 to have an unfavourable outcome 6 months after head injury. Further studies are under way to confirm and further evaluate this association.