Increased risk of late posttraumatic seizures associated with inheritance of APOE epsilon4 allele

Topic: Brain proteins, microglia and lab models

Background Late posttraumatic seizures are a common complication of moderate and severe traumatic brain injury. Inheritance of the apolipoprotein E (APOE) epsilon4 allele is associated with increased risk of Alzheimer disease, progression to disability in multiple sclerosis, and poor outcome after traumatic brain injury. Objective To determine whether inheritance of APOE epsilon4 is associated with increased risk of developing late posttraumatic seizures. Design Prospective study. Setting Neurosurgical service at an urban level I trauma center.Patients Patients admitted with a diagnosis of moderate and severe traumatic brain injury were enrolled. Methods Six months after injury, patients were contacted to determine functional outcome (according to the Glasgow Outcome Scale-Expanded [GOS-E]) and the presence of late posttraumatic seizures. Genotype at the APOE locus was determined by restriction fragment length polymorphism analysis. Results DNA and outcome information was obtained from 106 subjects. Six months after injury, 31 (29%) had a poor outcome (GOS-E score, 1-4), 47 (44%) had an intermediate outcome (GOS-E score, 5-6), and 28 (26%) had a favorable outcome (GOS-E score, 7-8). Twenty-one patients (20%) had at least 1 late posttraumatic seizure. The relative risk of late posttraumatic seizures for patients with the epsilon4 allele was 2.41 (95% confidence interval, 1.15-5.07; P =.03). In this cohort, inheritance of APOE epsilon4 was not associated with an unfavorable GOS-E score 6 (P =.47). Conclusions Inheritance of the APOE epsilon4 allele is associated with increased risk of late posttraumatic seizures. In this cohort, this risk appears to be independent of an effect of epsilon4 on functional outcome. A better understanding of the molecular role of APOE in neurodegenerative diseases may be helpful in developing antiepileptogenic therapies.

@article{diazarrastia2003-12810485,
  author  = {Diaz-Arrastia, R. and Gong, Y. and Fair, S. and Scott, K. D. and Garcia, M. C. and Carlile, M. C. and Agostini, M. A. and Van Ness, P. C.},
  title   = {{Increased risk of late posttraumatic seizures associated with inheritance of APOE epsilon4 allele}},
  journal = {Archives of neurology},
  year    = {2003},
  doi     = {10.1001/archneur.60.6.818},
  pmid    = {12810485},
  url     = {https://doi.org/10.1001/archneur.60.6.818}
}

Key findings

• Inheritance of the apolipoprotein E (APOE) epsilon4 allele is associated with increased risk of Alzheimer disease, progression to disability in multiple sclerosis, and poor outcome after traumatic brain injury.
• Objective To determine whether inheritance of APOE epsilon4 is associated with increased risk of developing late posttraumatic seizures.
• Results DNA and outcome information was obtained from 106 subjects.
• In this cohort, inheritance of APOE epsilon4 was not associated with an unfavorable GOS-E score 6 (P =.47).
• Conclusions Inheritance of the APOE epsilon4 allele is associated with increased risk of late posttraumatic seizures.

Why it matters

In 106 patients with moderate to severe traumatic brain injury, inheriting the APOE epsilon 4 allele was associated with a 2.41-fold higher relative risk of late posttraumatic seizures. The study did not find that epsilon 4 was associated with an unfavorable functional outcome overall.

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Study details

• Participants106
• Evidence strengthModerate

Read the original

• DOI: 10.1001/archneur.60.6.818
• PubMed: 12810485
• Original source →

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Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families Science · 1993-08-13 · usefulness score 63/100 · Genetics
• Association between apolipoprotein E genotype and Alzheimer disease in African American subjects Archives of neurology · 2002-04-01 · usefulness score 58/100 · Genetics
• The apolipoprotein epsilon 4 allele in patients with Alzheimer's disease Annals of neurology · 1993-11-01 · usefulness score 55/100 · Disparities

Later studies that cite this one

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• Comorbidities of epilepsy: current concepts and future perspectives The Lancet. Neurology · 2015-11-06 · usefulness score 56/100 · Caregiving
• Gene co-expression networks identify Trem2 and Tyrobp as major hubs in human APOE expressing mice following traumatic brain injury Neurobiology of disease · 2017-05-11 · usefulness score 40/100 · TREM2 and immune genetics
• Down syndrome, Alzheimer's disease and seizures Brain & development · 2005-06-01 · usefulness score 40/100 · Down syndrome and Alzheimer's

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• The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics JAMA · 1998-03-01 · usefulness score 70/100
• Altered brain white matter integrity in healthy carriers of the APOE epsilon4 allele: a risk for AD? Neurology · 2006-04-01 · usefulness score 49/100
• Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease Proceedings of the National Academy of Sciences of the United States of America · 1993-03-01 · usefulness score 58/100
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