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Association between SCN1A gene polymorphisms and drug resistant epilepsy in pediatric patients. | LitMetric
Purpose : "Single Nucleotide Polymorphisms (SNPs)" could be an important explanation of drug resistance in epilepsy. The aim of this study was to investigate if genetic polymorphisms (SNPs) of the SCN1A gene could influence the response to anti - epileptic drugs (AED) and if they could predispose to a drug resistant epilepsy in pediatric patients.Methods : We investigated SNPs in exon and intronic regions of the SCN1A gene in a sample of 120 pediatric patients, in both drug-resistant and drug-responsive patients. Association between polymorphisms and refractory epilepsy were investigated by comparing SNPs in exon and intronic regions between the two groups. The genotypes of each intronic polymorphism in the drug-resistant group was analyzed. Odds ratios and confidence intervals were calculated.Results : None of the SNPs identified in exons of the SCN1A gene were associated with drug-resistance. In the intronic regions, a statistically significant difference was found in the prevalence of three polymorphisms was found between the two patient groups (rs6730344A/C, rs6732655A/T, rs10167228A/T). The analysis of the genotypes of each intronic polymorphism in the drug-resistant group revealed that the AA and AT genotypes for the rs1962842 polymorphism are associated with an increased risk of developing drug resistance compared to TT genotype.Conclusion : The intronic rs6730344, rs6732655 and rs10167228 polymorphisms of the SCN1A gene are a potential risk factors for drug resistance. AA e AT genotype of the rs1962842 intronic polymorphism also emerged as a risk factor in the drug resistant group. Therefore, polymorphisms of the SCN1A gene could play a role in the response to AED in patients with drug-resistant epilepsy, with important implications for clinical practice.
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