机构：[a]Department of Neurology, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China临床科室泌尿外科小儿神经科首都医科大学附属北京儿童医院[b]Department of Pediatrics, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China首都医科大学附属天坛医院[c]Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China职能科室医技科室药学部药学部/药剂科首都医科大学附属天坛医院[d]Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing 100045, China
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% Cl: 0.095 to 0.79, P=0.017) and rs10188577 (SCNIA, 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 SCNIA genes were associated with seizure reduction. Larger studies are warranted to corroborate the results. (C) 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81301118]; Capital Medical University, China [PYZ2017113]; Beijing Municipal Administration of Hospitals, China [ZYLX201808]
第一作者机构：[a]Department of Neurology, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China[b]Department of Pediatrics, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China
共同第一作者：
通讯作者：
通讯机构：[a]Department of Neurology, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China[c]Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China[d]Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing 100045, China[*1]Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, 6 Tiantan Xili, Dongcheng District, Beijing 100050, China[*2]Department of Neurology, Beijing Children’s Hospital, Capital Medical University, 56 Nanlishi Road, Xicheng District, Beijing 100045, China.
推荐引用方式(GB/T 7714)：
Weixing Feng,Shenghui Mei,Leting Zhu,et al.Effects of UGT2B7, SCN1A and CYP3A4 on the therapeutic response of sodium valproate treatment in children with generalized seizures[J].SEIZURE-EUROPEAN JOURNAL OF EPILEPSY.2018,58:96-100.doi:10.1016/j.seizure.2018.04.006.
APA：
Weixing Feng,Shenghui Mei,Leting Zhu,Yazhen Yu,Weili Yang...&Fang Fang.(2018).Effects of UGT2B7, SCN1A and CYP3A4 on the therapeutic response of sodium valproate treatment in children with generalized seizures.SEIZURE-EUROPEAN JOURNAL OF EPILEPSY,58,
MLA：
Weixing Feng,et al."Effects of UGT2B7, SCN1A and CYP3A4 on the therapeutic response of sodium valproate treatment in children with generalized seizures".SEIZURE-EUROPEAN JOURNAL OF EPILEPSY 58.(2018):96-100
