Acta Neurochir (2003) 145: 649–654 DOI 10.1007/s00701-003-0069-3 Clinical Article Association between apolipoprotein E genotype and outcome of traumatic brain injury M.-F. Chiang 1 , J.-G. Chang 2 , and C.-J. Hu 3 1 Department of Neurosurgery, Mackay Memorial Hospital, Mackay Junior College of Nursing, Taipei, Taiwan 2 Department of Molecular Medicine, China Medical College, Taichung, Taiwan 3 Department of Neurology, Taipei Municipal Jen-Ai Hospital, Taipei, Taiwan Published online July 23, 2003 # Springer-Verlag 2003 Summary Background. The prognosis of traumatic brain injury is quite variable and not fully explained by the known factors. This study is to examine if the polymorphism of apolipoprotein E (apoE) influences the outcome of traumatic brain injury. Methods. Over a period of twelve months, we prospectively studied 100 patients who sustained traumatic brain injuries and were admitted to our neurosurgical unit. Findings. Nineteen patients were apoE4(þ) and 81 patients were apoE4(). There was no significant difference between apoE4(þ) and apoE4() groups in the cause of injury (p ¼ 0.288), type of brain injury (p ¼ 0.983) and choice of treatment (p ¼ 0.88). The proportion of patients with a lower GCS (<13), indicating a poor prognosis, was higher in the apoE4(þ) group (73.7%) than that in apoE4() group (61.7%), although the difference was not significant (p ¼ 0.654). Six patients (7.4%) in the apoE4() group and 5(26.3%) in the apoE4(þ) group had been drinking alcohol at the time of injury (p ¼ 0.018). The mean duration of hospital stay for apoE4(þ) patients was significantly longer than for apoE4() patients (p < 0.001). Six months after injury, 10 of 19 patients (52.6%) with apoE4 had an unfavorable outcome (dead, vegetative state, or severe disability) compared with 20 of the 81 (24.1%) patients without apoE4 (p ¼ 0.017). The apoE4(þ) patients had a significantly longer hospital stay and unfavorable outcomes after brain injury. Interpretation. This study discloses a significant genetic association between the apoE genotypes and outcomes of traumatic brain injury. Patients with apoE4 allele are more likely to have an unfavorable clinical outcome after brain injury. Keywords: Apolipoprotein E; genotype; PCR; traumatic brain injury. Introduction Apolipoprotein E (apoE), a 36,000 mol. wt. plasma glycolipoprotein, plays a key role in lipoprotein metab- olism by facilitating the cellular uptake of remnants of triglyceride-rich chylomicrons and very low density lipoproteins [2]. In humans, apoE, which is encoded by a four-exon gene and located on chromosome 19, has three isoforms (" 4, " 3 and " 2). Of these isoforms, " 4 is strongly linked to both sporadic and familial late- onset Alzheimer’s disease (AD) [2–4, 9, 11, 18, 22, 27]. In vitro data have shown substantial differences in the behavior of these isoforms [18, 30]. These genetic find- ings and the role of apoE in neuronal repair raise the possibility that the allele-specific effects of apoE may be due to dysfunction of the lipid-transport systems asso- ciated with sprouting and synaptic remodeling [2, 8, 18, 22]. Several studies of animal models show that apoE influences the neuronal response to acute brain injury [2, 7, 15, 22, 25, 30]. Furthermore Apo E genotype acts synergistically with a previous traumatic brain injury as risk factors for Alzheimer’s disease [4, 10, 12, 17, 19, 21, 24, 26, 29, 30]. The known prognostic factors, such as age, severity of injury and treatment, do not fully account for the vari- able outcome of a traumatic brain injury [16, 30]. The possibility that genetic variation among individuals may influence the response to brain injury and capacity for regeneration requires further investigation [30]. Several studies have reported that there are apoE genotype- dependent variations in the neuropathology of acute or chronic head injury [2, 8, 11, 19, 20]. Subsequent