Apolipoprotein E Genotype as an Independent Prognostic Factor for Clinical Outcome in Traumatic Brain Injury in Children and the Adolescent Population

Authors: E. Brichtová;  Z. Mackerle
Authors‘ workplace: Neurochirurgické oddělení Kliniky dětské chirurgie, ortopedie a traumatologie LF MU a FN Brno
Published in: Cesk Slov Neurol N 2011; 74/107(4): 437-442
Category: Original Paper


In the light of available published data, the authors considered the prospects of worse clinical outcome after brain injury more likely for patients possessing the 4 apolipoprotein E allele in both the paediatric and adolescent populations. The aim was to examine this hypo­thesis by means of a cohort of paediatric and adolescent patients with cerebral injuries. Materials and method: The presence of apolipoprotein E genotype was investigated in a group of 82 paediatric and adolescent patients who had suffered traumatic brain injury. The severity of trauma was assessed by the Glasgow coma scale. Clinical outcome after one year was assessed by the extended Glasgow outcome scale. Severity of injury was compared with clinical outcome after one year with respect to apolipoprotein E genotype and evaluated statistically using the Wilcoxon nonparametric test, Student’s t-test, χ2 and Fischer tests. Results: Analysis of the data obtained confirmed a relationship between the presence of ε4 apolipo­protein E allele and worse clinical course after brain injury in children and adolescents. Children and adolescent patients possessing the ε4 apolipoprotein E allele have a higher risk of unfavourable clinical outcome after serious brain injury, compared to a significantly better outcome in patients with other apolipoprotein E alleles. Conclusions: Apolipoprotein E genotype is an independent prognostic factor for clinical outcome in traumatic brain injury in children and the adolescent population.

Key words:
apolipoprotein E – cerebral injury – Glasgow Coma Scale – Extended Glasgow Outcome Scale – paediatric population – adolescent population


1. Nathoo N, Chetty R, van Dellen JR, Barnett GH. Genetic vulnerability following traumatic brain injury: the role of apolipoprotein E. Mol Pathol 2003; 56(3): 132–136.

2. Samatovicz RA. Genetics and brain injury: apolipoprotein E. Head Trauma Rehabil 2000; 15(3): 869–874.

3. Graham DI, Ford I, Adams JH, Doyle D, Lawrence AE, McLellan DR et al. Fatal head injury in children. J Clin Pathol 1989; 42(1): 18–22.

4. Graham DI, Horsburgh K, Nicoll JA, Teasdale GM. Apolipoprotein E and the response of the brain to injury. Acta Neurochir Suppl 1999; 73: 89–92.

5. Methia N, Andre P, Hafezi-Moghadam A, Economopoulos M, Thomas KL, Wagner DD. Apo E deficiency compromises the blood brain barrier especially after injury. Mol Med 2001; 7(12): 810–815.

6. Kerr ME, Kraus M. Genetics and the central nervous system: apolipoprotein E and brain injury. AACN Clin Issues 1998; 9(4): 524–530.

7. Crawford FC, Vanderploeg RD, Freeman MJ, Singh S, Waisman M, Michaels L et al. APOE genotype influences acquisition and recall following traumatic brain injury. Neurology 2002; 58(7): 1115–1118.

8. Friedman G, Froom P, Sazbon L, Grinblatt I, Shochina M, Tsenter J et al. Apolipoprotein E-epsilon4 genotype predicts a poor outcome in survivors of traumatic brain injury. Neurology 1999; 52(2): 244–248.

9. Schiefermeier M, Kollegger H, Madl C, Schwarz C, Holzer M, Kofler J et al. Apolipoprotein E polymorphism: survival and neurological outcome after cardio­pulmonary resuscitation. Stroke 2000; 31(9): 2068–2073.

10. Horsburgh K, McCarron MO, White F, Nicoll JA. The role of apolipoprotein E in Alzheimer’s disease, acute brain injury and cerebrovascular disease: evidence of common mechanisms and utility of animal models. Neurobiol Aging 2000; 21(2): 245–255.

11. Lendon CL, Harris JM, Pritchard AL, Nicoll JA, Teasdale GM, Murray G. Genetic variation of the APOE promoter and outcome after head injury. Neurology 2003; 61(5): 683–685.

12. Dardiotis E, Fountas KN, Dardioti M, Xiromerisiou G, Kapsalaki E, Tasiou A et al. Genetic association studies in patients with traumatic brain injury. Neurosurg Focus 2010; 28(1): E9.

13. Lomnitski L, Kohen R, Chen Y, Shohami E, Trembovler V, Vogel et al. Reduced levels of anti­oxidants in brains of apolipoprotein E-deficient mice following closed head injury. Pharmacol Biochem Behav 1997; 56(4): 669–673.

14. Miyata M, Smith JD. Apolipoprotein E allele– specific antioxidant activity and effect on cytotoxicity by oxidantive insults and beta amyloid peptides. Nat Genet 1996; 14(1): 55–61.

15. Tolar M, Keller JN, Chan S, Mattson MP, Marques MA, Crutcher KA. Truncated apolipoprotein E (ApoE) causes increased intracellular calcium and may mediate ApoE neurotoxicity. J Neurosci 1999; 19(16): 7100–7110.

16. Barger SW, Harmon AD. Microglial activation by Alzheimer amyloid precursor protein and modulation of apolipoprotein. Nature 1997; 388(6645): 878–881.

17. Hixson JE. Apolipoprotein E polymorphism affect atherosclerosis in young males. Pathobiological determinations of atherosclerosis in youth (PDAY) research group. Arterioscler Thromb 1991; 11(5): 1237–1244.

18. Lynch JR, Pineda JA, Morgan D, Zhang L, Warner DS, Benveniste H et al. Apolipoprotein E affects the central nervous system response to injury and development of cerebral edema. Ann Neurol 2002; 51(1): 113–117.

19. Kozák L, Kuhrová V, Blazková M, Romano V, Fajkusová L, Dvoráková D et al. Phenylketonuria mutations and their relation to RFLP haplotypes at the PAH locus in Czech PKU families. Hum Genet 1995; 96(4): 472–476.

20. Chiang MF, Chang JG, Hu CJ. Association between apolipoprotein E genotype and outcome of traumatic brain injury. Acta Neurochir 2003; 145(8): 649–653.

21. Friedman G, Froom P, Sazbon L, Grinblatt I, Shochina M, Tsenter J et al. Apolipoprotein E-epsilon4 genotype predicts a poor outcome in survivors of traumatic brain injury. Neurology 1999; 52(2): 244–248.

22. Jordan BD, Relkin NR, Ravdin LD, Jacobs AR, Bennett A, Gandy S. Apolipoprotein E epsilon 4 associated with chronic brain injury in boxing. JAMA 1997; 278(2): 136–140.

23. Krupa M, Moskala M, Gościński I, Traczewski W, Polak J, Sado M. Association of apoE polymorphism and treatment outcome in patients with traumatic brain injury. Neurol Neurochir Pol 2003; 37(6): 1223–1229.

24. Teasdale GM, Nicoll JA, Murray G, Fiddes M. Association of apolipoprotein E polymorphism with outcome after head injury. Lancet 1997; 350(9084): 1069–1071.

25. Leclercq PD, Murray LS, Smith C, Graham DI, Nicoll JA, Gentleman SM. Cerebral amyloid angio­pathy in traumatic brain injury: association with apolipoprotein E genotype. J Neurol Neurosurg Psychiatry 2005; 76(2): 229–233.

26. Nicoll JA, Roberts GW, Graham DI. Apolipoprotein E epsilon 4 allele is associated with deposition of amyloid beta-protein following head injury. Nat Med 1995; 1(2): 135–137.

27. Alberts MJ, Graffagnino C, McClenny C, DeLong D, Strittmatter WJ, Saunders AM et al. ApoE genotype and survival from intracerebral haemorrhage. Lancet 1995; 346(8974): 575.

28. McCarron MO, Hoffmann KL, DeLong DM , Gray L , Saunders AM , Alberts MJ. Intracerebral hemorrhage outcome, apolipoprotein E genotype, hematoma, and edema volumes. Neurology 1999; 53(9): 2176–2179.

29. Liaquat I, Dunn LT, Nicoll JA, Teasdale GM, Norrie JD. Effect of apolipoprotein E genotype on hematoma volume after trauma. J Neurosurg 2002; 96(1): 90–96.

30. Nicoll JA, Roberts GW, Graham DI. Amyloid beta-protein, APOE genotype and head injury. Ann N Y Acad Sci 1996; 777: 271–275.

31. Kay AD, Petzold A, Kerr M, Keir G, Thompson E, Nicoll J et al. Alterations in cerebrospinal fluid apolipoprotein E and amyloid beta-protein after traumatic brain injury. J Neurotrauma 2003; 20(10): 943–952.

32. Bartzokis G, Lu PH, Sultzer D, Marx P, Herzberg JS, Phelan CK et al. Apolipoprotein E genotype and age-related myelin breakdown in healthy individuals: implications for cognitive decline and dementia. Arch Gen Psychiatry 2006; 63(1): 63–72.

33. Koponen S, Taiminen T, Kairisto V, Portin R, Isoniemi H, Hinkka S et al. APOE-epsilon4 predicts dementia but not other psychiatric disorders after traumatic brain injury. Neurology 2004; 63(4): 749–750.

34. Chamelian L, Reis M, Feinstein A. Six-month recovery from mild to moderate Traumatic Brain Injury: the role of APOE-epsilon 4 allele. Brain 2004; 127(12): 2621–2628.

35. Pruthi N, Chandramouli BA, Kuttappa TB, Rao SL, Subbakrishna DK, Abraham MP et al. Apolipoprotein E polymorphism and outcome after mild to moderate traumatic brain injury: A study of patient population in India. Neurology India 2010; 58(2): 264–269.

36. Collie A, Maruff P, Falleti M. APOE influences on neuropsychological function after mild head injury: Within-person comparisons. Neurology 2004; 63(12): 2460.

37. Sundstrom A, Marklund P, Nilsson LG, Cruts M, Adolfsson R, Van Broeckhoven C et al. APOE influences on neuropsychological function after mild head injury: within-person comparisons. Neurology 2004; 62(11): 1963–1966.

38. Diaz-Arrastia R, Gong Y, Fair S, Scott KD, Garcia MC, Carlile MC et al. Increased risk of late posttraumatic seizures associated with inheritance of APOE epsilon 4 allele. Arch Neurol 2003; 60(6): 818–822.

Paediatric neurology Neurosurgery Neurology

Article was published in

Czech and Slovak Neurology and Neurosurgery

2011 Issue 4

Most read in this issue
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account