机构：[1]Department of Neurology, Beijing Children’s Hospital, Capital Medical University, Beijing, People’s Republic of 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[2]Department of Pediatrics, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China首都医科大学附属天坛医院[3]Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of 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[4]Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China
Objective This study aims to describe the associations between genetic polymorphisms and therapeutic effect of valproic acid (VPA) in children with focal seizures. Methods Eighty-nine children with focal seizures on VPA therapy were enrolled. Patients' basic information, dosage regimens, and plasma concentrations were recorded. A 1-year follow-up was performed to evaluate the treatment response. Sixty-six single nucleotide polymorphisms involved in the metabolism, transport, and target receptor of VPA were identified, and their associations with VPA response were analyzed using logistic regression adjusted by various influence factors. Selected polymorphisms involved in the metabolism, transport, and target receptor of VPA were not associated with treatment effect in children with focal seizures. Results Three variants, rs9313892 (GABRA6, G > A, OR = 2.73, 95% CI 1.00 to 7.48, P = 0.051), rs4921195 (GABRA6, T > C, OR = 2.71, 95% CI 0.99 to 7.42, P= 0.053), and rs424740 (GABRG2, A > T, OR = 0.39, 95% CI 0.15 to 1.01, P= 0.053) had the potential to be associated with the VPA response. Conclusion Selected genetic polymorphisms were not significantly associated with VPA response in children with focal seizures. However, three GABR variants showed potential to be associated with the response to VPA. Further and larger studies are warranted to confirm the results.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81301118]
第一作者机构：[1]Department of Neurology, Beijing Children’s Hospital, Capital Medical University, Beijing, People’s Republic of China[2]Department of Pediatrics, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Neurology, Beijing Children’s Hospital, Capital Medical University, Beijing, People’s Republic of China[3]Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China[4]Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China
推荐引用方式(GB/T 7714)：
Feng Weixing,Mei Shenghui,Han Jiaqi,et al.Lack of association between valproic acid response and polymorphisms of its metabolism, transport, and receptor genes in children with focal seizures[J].NEUROLOGICAL SCIENCES.2019,40(3):523-528.doi:10.1007/s10072-018-3681-y.
APA：
Feng, Weixing,Mei, Shenghui,Han, Jiaqi,Zhu, Leting,Yu, Yazhen...&Fang, Fang.(2019).Lack of association between valproic acid response and polymorphisms of its metabolism, transport, and receptor genes in children with focal seizures.NEUROLOGICAL SCIENCES,40,(3)
MLA：
Feng, Weixing,et al."Lack of association between valproic acid response and polymorphisms of its metabolism, transport, and receptor genes in children with focal seizures".NEUROLOGICAL SCIENCES 40..3(2019):523-528
