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Abstract：
Background and Objectives: Drug resistant epilepsy (DRE) is a major hurdle in epilepsy, which hinders clinical care, patients\' management and treatment outcomes. DRE may partially result from genetic variants that alter proteins responsible for drug targets and drug transporters in the brain. We aimed to examine the relationship between SCN1A, GABRA1 and ABCB1 polymorphism and drug response in epilepsy children in Vietnam. Materials and Methods: In total, 213 children diagnosed with epilepsy were recruited in this study (101 were drug responsive and 112 were drug resistant). Sanger sequencing had been performed in order to detect six single nucleotide polymorphisms (SNPs) belonging to SCN1A (rs2298771, rs3812718, rs10188577), GABRA1 (rs2279020) and ABCB1 (rs1128503, rs1045642) in study group. The link between SNPs and drug response status was examined by the Chi-squared test or the Fisher\'s exact test. Results: Among six investigated SNPs, two SNPs showed significant difference between the responsive and the resistant group. Among those, heterozygous genotype of SCN1A rs2298771 (AG) were at higher frequency in the resistant patients compared with responsive patients, playing as risk factor of refractory epilepsy. Conversely, the heterozygous genotype of SCN1A rs3812718 (CT) was significantly lower in the resistant compared with the responsive group. No significant association was found between the remaining four SNPs and drug response. Conclusions: Our study demonstrated a significant association between the SCN1A genetic polymorphism which increased risk of drug-resistant epilepsy in Vietnamese epileptic children. This important finding further supports the underlying molecular mechanisms of SCN1A genetic variants in the pathogenesis of drug-resistant epilepsy in children.
摘要：
背景和目的:耐药癫痫(DRE)是癫痫的一大障碍,这阻碍了临床护理，患者管理和治疗结果。DRE可能部分是由改变大脑中负责药物靶标和药物转运蛋白的遗传变异产生的。我们的目的是检验SCN1A，越南癫痫儿童的GABRA1和ABCB1多态性与药物反应。材料和方法：总计，本研究招募了213名被诊断为癫痫的儿童（101名对药物有反应，112名耐药）。进行Sanger测序以检测属于SCN1A的六个单核苷酸多态性（SNP）（rs2298771，rs3812718，rs10188577），研究组GABRA1(rs2279020)和ABCB1(rs1128503,rs1045642)。通过卡方检验或Fisher精确检验检查SNP与药物反应状态之间的联系。结果：在六个调查的SNP中，两个SNP在应答组和抗性组之间显示出显着差异。其中,SCN1Ars2298771（AG）的杂合基因型在耐药患者中的频率较高，作为难治性癫痫的危险因素。相反，与反应组相比，耐药组的SCN1Ars3812718（CT）的杂合子基因型显着降低。其余四个SNP与药物反应之间没有发现显着关联。结论：我们的研究表明，SCN1A基因多态性之间存在显着关联，这增加了越南癫痫儿童的耐药性癫痫风险。这一重要发现进一步支持了SCN1A遗传变异在儿童耐药性癫痫发病机制中的潜在分子机制。
