Association of apolipoprotein E genotypes with epilepsy risk: A systematic review and meta-analysis

Epilepsy Behav. 2019 Sep;98(Pt A):27-35. doi: 10.1016/j.yebeh.2019.06.015. Epub 2019 Jul 9.

Abstract

Objective: The objective of this study was to identify the association between certain genotypes or alleles of the APOE (Apolipoprotein E) gene and the epilepsy risk.

Methods: All studies on human APOE genotypes associated with epilepsy were included. Separate meta-analyses were conducted between the patients with epilepsy and the control group from the following three aspects: ε4 carriers or ε2 carriers vs ε3/ε3 (the ε2/ε4 genotype was excluded), ε4 carriers vs ε2 carriers, and five genotypes vs ε3/ε3. The subgroup analysis was conducted on the ethnicity, the control group was healthy or not, and type of epilepsy.

Results: Nine studies with 2210 individuals were included. Compared with ε3/ε3 genotype, ε4 carriers increased the epilepsy risk (odds ratios [ORs]: 1.27; 95% confidence intervals [CI]: 1.01 to 1.59; P = 0.042), while ε2 carriers had no association with epilepsy risk (OR: 0.88; 95% CI: 0.66 to 1.18; P = 0.184). The risk of epilepsy was 1.45 times greater in ε4 carriers compared with ε2 carriers (OR: 1.45; 95% CI: 1.02 to 2.04; P = 0.037). When the number of APOE ε4 allele increased, the ORs increased progressively (no ε4 alleles, OR: 0.88, 95% CI: 0.66 to 1.18; one ε4 allele, OR: 1.25, 95% CI: 0.99 to 1.57; two ε4 alleles, OR: 1.84, 95% CI: 0.83 to 4.10). Apolipoprotein E ε4 carriers had a higher epilepsy risk in the population without primary diseases (OR: 1.43; 95% CI: 1.09 to 1.88), and a higher risk in Asian populations (OR: 1.67; 95% CI: 1.12 to 2.49).

Conclusions: Apolipoprotein E ε4 allele genotype was associated with an increased epilepsy risk, which was more prominent in the Asian and the population without primary diseases. These findings may be used to guide the directions of prevention and treatment on epilepsy. Larger clinical studies are needed.

Keywords: Apolipoprotein E; Epilepsy; Genotypes; Meta-analysis; Risk.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Alleles
  • Apolipoproteins E / genetics*
  • Asian People / genetics
  • Epilepsy / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Heterozygote
  • Humans
  • Risk Factors

Substances

  • Apolipoproteins E