Association of apolipoprotein E polymorphism with outcome after head injury

Abstract

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 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.

Methods: 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.

Findings: 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).

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 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.