Characterization of a single nucleotide polymorphism in the microRNA-146a and epilepsy susceptibility

Abstract

Epilepsy has been described as the fourth most common neurological disease, affectting until 2% of world population that represents around 50 milions of patients. The authors showed a gap in the literature regarding the evaluation of the susceptibility of the epileptic development and the characterization of genetic alterations in the epileptic tissue. Although some studies have described miRNA146a involved in epileptogenesis through the regulation of inflammatory pathway, there are no studies in the Brazilian population about the relationship between single nucleotide polymorphism (SNP) in the MIR146a gene n.60G> C (rs2910464) and the risk of epilepsy. Objectives: To evaluate the MIR146a SNP n.60G> C as a risk factor and prognosis in patients affected by clinically refractory epilepsy. Methods: Patients affected by medically refractory epilepsy treated by selective amygdalohipocampectomy surgical approach will be retrospectively selected. The collection of clinical data will be carried out by registration in medical records. The study will be conducted on DNA samples extracted from epilephogenic tissue from patients with refractory epilepsy and on DNA samples extracted from peripheral blood leukocytes from healthy blood donors. DNA extraction followed by the real-time polymerase chain reaction (RT-PCR) will be performed to identify genotypes of the n.60G> C polymorphism in MIR146a. Furthermore, the expression of MIR146a in the different identified SNP genotypes will be evaluated by qPCR, as well as the expression of genes belonging to the NF-kB pro-inflammatory signaling pathway, such as IRAK-1, IRAK-2 and TRAF-6. The significance level pd0.05 will be adopted in the analysis of the results.