European Journal of Clinical Pharmacology

, Volume 75, Issue 5, pp 655–663 | Cite as

SCN1A and SCN2A polymorphisms are associated with response to valproic acid in Chinese epilepsy patients

  • Lihong Shi
  • Miaomiao Zhu
  • Huilan Li
  • Zhipeng Wen
  • Xiaoping Chen
  • Jia Luo
  • Cong Lin
  • Zanling ZhangEmail author



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.

Trial registration



Epilepsy Valproic acid SCN1A SCN2A Antiepileptic efficacy 



We thank all patients and their family members who contributed to this work. We thank Professor Shusen Sun from College of Pharmacy and Health Sciences at Western New England University, USA, for his valuable advice.

Contributions of authors

Zanling Zhang designed the study. Lihong Shi performed the data analysis and wrote the manuscript. Miaomiao Zhu, Huilan Li, and Zhipeng Wen recruited patients and conducted patients’ follow-up. Jia Luo and Cong Lin extracted the DNA. Xiaoping Chen reviewed the manuscript and critically revised the intellectual content of the manuscript.

Funding information

This work was supported by a grant from the Natural Science Foundation of Hunan Province (no. 2017JJ2398).

Compliance with ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of Xiangya Hospital Central South University Medical Ethics Committee, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

228_2019_2633_MOESM1_ESM.docx (19 kb)
ESM 1 (DOCX 19 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmacy, Xiangya HospitalCentral South UniversityChangshaChina
  2. 2.Institute of Hospital PharmacyCentral South UniversityChangshaChina
  3. 3.Department of Clinical Pharmacology, Xiangya HospitalCentral South UniversityChangshaChina
  4. 4.Institute of Clinical PharmacologyCentral South UniversityChangshaChina

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