Department of Pharmacy, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, 410008, Hunan, China.
Institute of Hospital Pharmacy, Central South University, No. 87 Xiangya Road, Changsha, 410008, Hunan, China.
Eur J Clin Pharmacol. 2019 May;75(5):655-663. doi: 10.1007/s00228-019-02633-0. Epub 2019 Jan 28.
There is a large inter-individual variation in the efficacy of valproic acid (VPA) against epilepsy. The genetic polymorphism influence of sodium channels on VPA response remains a matter of debate. The aim of the study was to explore the effect of SCN1A and SCN2A gene polymorphisms on VPA response in the treatment of epilepsy among Chinese patients.
A total of 354 epileptic patients with VPA treatment were genotyped for five single nucleotide polymorphisms (SNP), including SCN1A rs10188577 T>C, rs2298771 T>C, rs3812718 G>A, and SCN2A rs2304016 A>G, rs17183814 G>A. A binary logistic regression analysis was performed to evaluate the association of genotype with VPA antiepileptic effects, adjusting the influence of confounding factors.
Genotype distributions of all selected SNPs were consistent with the Hardy-Weinberg equilibrium in epilepsy patients. SCN1A rs3812718 and SCN2A rs2304016 were found to be significantly associated with VPA response, both in monotherapy and in VPA-based polytherapy. Patients with the rs3812718 A allele were more frequently seen in the VPA-responsive group (P < 0.05), and the rs2304016 G allele was related to an increased risk of resistance to VPA therapy (P < 0.05).
Our study revealed that SCN1A rs3812718 and SCN2A rs2304016 polymorphisms might be markers of VPA response in Chinese epilepsy patients.
ChiCTR-1800016477.
丙戊酸（VPA）治疗癫痫的疗效存在很大的个体间差异。钠离子通道的遗传多态性对 VPA 反应的影响仍然存在争议。本研究旨在探讨 SCN1A 和 SCN2A 基因多态性对中国患者癫痫 VPA 治疗反应的影响。
对 354 例 VPA 治疗的癫痫患者进行了 5 个单核苷酸多态性（SNP）的基因分型，包括 SCN1A rs10188577 T>C、rs2298771 T>C、rs3812718 G>A 和 SCN2A rs2304016 A>G、rs17183814 G>A。采用二元逻辑回归分析评估基因型与 VPA 抗癫痫作用的关系，调整混杂因素的影响。
所有选定 SNP 的基因型分布均符合癫痫患者的 Hardy-Weinberg 平衡。SCN1A rs3812718 和 SCN2A rs2304016 与 VPA 反应均显著相关，无论是单药治疗还是 VPA 联合治疗。VPA 反应组患者更常见 rs3812718 A 等位基因（P<0.05），rs2304016 G 等位基因与 VPA 治疗耐药风险增加相关（P<0.05）。
本研究表明，SCN1A rs3812718 和 SCN2A rs2304016 多态性可能是中国癫痫患者 VPA 反应的标志物。
ChiCTR-1800016477。
