The single nucleotide variant n.60 G > C in the microRNA-146a associated with susceptibility to drug-resistant epilepsy

Abstract Objective The aim of this study was to evaluate single nucleotide variants (SNVs) n.-411A > G (rs57095329) and n.60 G > C (rs2910164) in microRNA (miR)-146a, related to suppressing of TRAF6 with risk for epilepsy, as well as miR-146a and TRAF6 levels. Methods DNAs were extracted from epileptogenic tissues and blood leukocytes from drug-resistant epilepsy patients and healthy-individuals, respectively. Genotypes were identified by real-time PCR. Hardy-Weinberg equilibrium (HWE) and Fisher or X2 tests evaluated the difference between groups. The disease risk was assessed by odds ratio (OR) with 95% confidence interval (95%CI). The prognostic impact on probability seizure-free survival (PSF) was evaluated by Kaplan-Meier and log-rank tests. Results For rs57095329 both control and patient samples were not in HWE (p  0.05). For rs2910164, samples were in HWE (p = 0.61), contrasting with patients (p = 0.03), and similar frequencies of wild-type homozygous (GG) (43.4% vs. 34.4%, p = 0.2) and variant (CC) genotypes (8.0% vs. 6.6%, p = 0.6) were observed in patients and controls, respectively. However, increased frequency of heterozygous (GC) was observed in patients compared to controls (59.0% vs. 42.7%, p = 0.04) with 1.98 (95%CI=1.09-3.57) risk for epilepsy. The miR-146a expression level in the epileptogenic tissues was lower in the GC (p = 0.02) and CC (p = 0.09) compared to GG genotype. TRAF6 expression level was higher in CC than in GG genotype (p = 0.09). Interestingly, there was an increased frequency of patients harboring GC genotype and less time until surgery compared to patients harboring GG or CC (36.06% vs. 11.5%, p = 0.01), confirmed by PSF (p = 0.04). Conclusions The GC genotype for SNV rs2910164 appears associated with susceptibility to drug-resistant epilepsy due to the decreased MIR146a expression, favoring NF-kB pathway through TRAF6.