Effects of UGT2B7, SCN1A and CYP3A4 on the therapeutic response of sodium valproate treatment in children with generalized seizures. (May 2018)

• Record Type: Journal Article
• Authors: Feng, Weixing; Mei, Shenghui; Zhu, Leting; Yu, Yazhen; Yang, Weili; Gao, Baoqin; Wu, Xiaojuan; Zhao, Zhigang; Fang, Fang
• Is Part Of: Seizure. Volume 58(2018)
• Page Start: 96
• Page End: 100
• Publication Date: 2018-05
• Subjects: VPA sodium valproate -- FABP2 fatty acid binding protein 2 -- ABCB1 ATP binding cassette subfamily B member 1 -- ABCC2 ATP binding cassette subfamily C member 2 -- GABA gamma-aminobutyric acid -- ABAT 4-aminobutyrate aminotransferase -- GABR GABA receptor -- SCN sodium voltage-gated channel -- NMDA N-methyl-d-aspartate -- GRIN glutamate ionotropic receptor NMDA type -- MAF minor allele frequency -- HWE Hardy-Weinberg equilibrium -- OR odds ratio -- 95% CI 95% confidence interval -- SNP single nucleotide polymorphism -- UGT2B7 uridine diphosphate glucuronosyltransferase family 2 member B7 -- CYP3A4 Cytochrome P450 family 3 subfamily A member 4 -- SCN1A sodium voltage-gated channel alpha subunit 1 -- CYP2C9 cytochrome P450 family 2 subfamily C member 9; Children -- Sodium valproate -- Generalized seizures -- Genetic polymorphisms -- Drug-resistant epilepsy; Epilepsy -- Periodicals; Epilepsy -- Periodicals; Seizures -- Periodicals; Épilepsie -- Périodiques; Electronic journals; Electronic journals; 616.853
• DOI: 10.1016/j.seizure.2018.04.006
• Languages: English
• ISSNs: 1059-1311

Abstract

Highlights: rs7668282 was more prevalent in drug-resistant patients than drug-responsive patients. rs2242480 and rs10188577 were more prevalent in drug-resistant patients than drug-responsive patients. Polymorphisms of UGT2B7, CYP3A4, and SCN1A genes were associated with VPA efficacy. Abstract: Purpose: This study aims to evaluate the associations between genetic polymorphisms and the effect of sodium valproate (VPA) therapy in children with generalized seizures. Methods: A total of 174 children with generalized seizures on VPA therapy were enrolled. Steady-state trough plasma concentrations of VPA were analyzed. Seventy-six single nucleotide polymorphisms involved in the absorption, metabolism, transport, and target receptor of VPA were identified, and their associations with the therapeutic effect (seizure reduction) were evaluated using logistic regression adjusted by various influence factors. Results: rs7668282 ( UGT2B7, T > C, OR = 2.67, 95% CI: 1.19 to 5.91, P = 0.017) was more prevalent in drug-resistant patients than drug-responsive patients. rs2242480 ( CYP3A4, C > T, OR = 0.27, 95% CI: 0.095 to 0.79, P = 0.017) and rs10188577 ( SCN1A, T > C, OR = 0.40, 95% CI: 0.17 to 0.94, P = 0.035) were more prevalent in drug-responsive patients compared to drug-resistant patients. Conclusion: In children with generalized seizures on VPA therapy, polymorphisms of UGT2B7, CYP3A4, and SCN1A genes were associated with seizure reduction. Larger studies are warranted to corroborate the results.