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

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: epsilon 4 carriers or epsilon 2 carriers vs epsilon 3/epsilon 3 (the epsilon 2/epsilon 4 genotype was excluded), epsilon 4 carriers vs epsilon 2 carriers, and five genotypes vs epsilon 3/epsilon 3. 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 epsilon 3/epsilon 3 genotype, epsilon 4 carriers increased the epilepsy risk (odds ratios [ORs]: 127; 95% confidence intervals [CI]: 1.01 to 1.59; P = 0.042), while epsilon 2 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 epsilon 4 carriers compared with epsilon 2 carriers (OR: 1.45; 95% CI: 1.02 to 2.04; P = 0.037). When the number of APOE epsilon 4 allele increased, the ORs increased progressively (no epsilon 4 alleles, OR: 0.88, 95% CI: 0.66 to 1.18; one epsilon 4 alleles, OR: 125, 95% CI: 0.99 to 1.57; two epsilon 4 alleles, OR: 1.84, 95% CI: 0.83 to 4.10). Apolipoprotein E epsilon 4 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 epsilon 4 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. (C) 2019 Elsevier Inc. All rights reserved.