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

Author(s)

Boschiero, Matheus Negri ^[1] ; Camporeze, Bruno ^[1] ; dos Santos, Jessica Silva ^[1] ; da Costa, Leandro Borsari ^[1] ; Bonafe, Gabriel Alves ^[1] ; Queiroz, Luciano de Souza ^[2] ; Van Roost, Dirk ^[3] ; Lima Marson, Fernando Augusto ^[1] ; Pires de Aguiar, Paulo Henrique ^{[1, 4, 5]} ; Ortega, Manoela Marques ^[1]

Affiliation

^[1] Sao Francisco Univ, Lab Cell & Mol Tumor Biol & Bioact Cpds, Med Sch USF, Braganca Paulista, SP - Brazil

^[2] Univ Estadual Campinas, Dept Pathol, Unicamp, Campinas, SP - Brazil

^[3] Ghent Univ Hosp, Dept Neurosurg, Ghent - Belgium

^[4] ABC Med Sch, Santo Andre, SP - Brazil

^[5] State Civil Servant Hosp IAMSPE, Dept Neurosurg, Postgrad Program, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Epilepsy Research; v. 162, MAY 2020.
• Web of Science Citations: 0

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 X-2 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) and the genotypes prevalence was similar in patients and controls (p > 0.05). For rs2910164, control 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. (AU)

• FAPESP's process: 18/12057-0 - Characterization of a single nucleotide polymorphism in the microRNA-146a and epilepsy susceptibility
• Grantee: Bruno Camporeze
• Support type: Scholarships in Brazil - Scientific Initiation