Lihong Shi1,2, Miaomiao Zhu1,2, Huilan Li1,2, Zhipeng Wen3,4, Xiaoping Chen3,4, Jia Luo1,2, Cong Lin1,2, Zanling Zhang5,6. 1. Department of Pharmacy, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, 410008, Hunan, China. 2. Institute of Hospital Pharmacy, Central South University, No. 87 Xiangya Road, Changsha, 410008, Hunan, China. 3. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, No. 110 Xiangya Road, Changsha, 410008, China. 4. Institute of Clinical Pharmacology, Central South University, No. 110 Xiangya Road, Changsha, 410008, China. 5. Department of Pharmacy, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, 410008, Hunan, China. zanlingzhang2015@126.com. 6. Institute of Hospital Pharmacy, Central South University, No. 87 Xiangya Road, Changsha, 410008, Hunan, China. zanlingzhang2015@126.com.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Our study revealed that SCN1A rs3812718 and SCN2A rs2304016 polymorphisms might be markers of VPA response in Chinese epilepsy patients. TRIAL REGISTRATION: ChiCTR-1800016477.
PURPOSE: 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. METHODS: A total of 354 epilepticpatients with VPA treatment were genotyped for five single nucleotide polymorphisms (SNP), including SCN1Ars10188577 T>C, rs2298771 T>C, rs3812718 G>A, and SCN2Ars2304016 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. RESULTS: Genotype distributions of all selected SNPs were consistent with the Hardy-Weinberg equilibrium in epilepsypatients. SCN1Ars3812718 and SCN2Ars2304016 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). CONCLUSIONS: Our study revealed that SCN1Ars3812718 and SCN2Ars2304016 polymorphisms might be markers of VPA response in Chinese epilepsypatients. TRIAL REGISTRATION: ChiCTR-1800016477.
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