Association of KEAP1 and NFE2L2 polymorphisms with temporal lobe epilepsy and drug resistant epilepsy

- A NFE2L2 gene haplotype increased risk of temporal lobe epilepsy.
- A variation in the NFE2L2 gene increased the risk of drug resistant epilepsy.
- A variation in the KEAP1 gene decreased the risk of drug resistant epilepsy.
- Synergistic effects of the NFE2L2 and KEAP1 genes on temporal lobe epilepsy and drug resistant epilepsy were not found.

Background and aimsTemporal lobe epilepsy (TLE) is a prevalent form of epilepsy. TLE contributes to the majority of drug resistant epilepsy (DRE) cases and is associated with genetic factors. Kelch-like ECH-associated protein 1 (KEAP1)/Nuclear erythroid 2-related factor 2 (known as NFE2L2 or Nrf2) association has been implicated in neuroprotection due to induction of antioxidant enzymes. The association of one single KEAP1 gene nucleotide polymorphism (SNP) and nine NFE2L2 gene SNPs with TLE and DRE were examined to determine whether these SNPs influenced the risk of TLE and DRE in a Han population.Subjects and methodsA total of 184 TLE patients (including 72 DRE patients) and 183 controls were included in this analysis. The SNaPshot Multiplex kit was used to assess the genotypes.ResultsA NFE2L2 gene haplotype was identified as a risk factor for TLE (OR = 7.11, 95% CI 1.53-32.98). Additionally, rs2706110 G > A in the NFE2L2 gene and rs1048290 C > G in the KEAP1 gene showed a significant risk for and a protective effect against DRE, respectively.ConclusionOur findings suggest that variations in NFE2L2 gene increase the risk of TLE and DRE but that variations in KEAP1 gene play a protective role for DRE.