This study aims to describe the associations between genetic polymorphisms and therapeutic effect of valproic acid (VPA) in children with focal seizures.
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.
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.
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.
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ATP binding cassette subfamily B member 1
ATP binding cassette subfamily C member 2
GABA type A receptor gamma 2 subunit
Sodium voltage-gated channel
Glutamate ionotropic receptor NMDA type
Minor allele frequency
- 95% CI:
95% confidence interval
Gamma-aminobutyric acid type A receptor alpha 6 subunit
Cytochrome P450 family 2 subfamily C member 9.
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Thanks to our patients and our whole team. Particularly grateful to professor Shiqi Peng, Ming Zhao, Yuji Wang (College of Pharmaceutical Science, Capital Medical University, Beijing, China), Jiawang Liu (Medicinal Chemistry Core, Division of Vice Chancellor for Research, University of Tennessee Health Science Center), and the reviewers for their help in manuscript revision.
This study was funded by the National Natural Science Foundation of China (no. 81301118).
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Weixing Feng, Shenghui Mei, and Jiaqi Han are equal first authors
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Feng, W., Mei, S., Han, J. et al. Lack of association between valproic acid response and polymorphisms of its metabolism, transport, and receptor genes in children with focal seizures. Neurol Sci 40, 523–528 (2019). https://doi.org/10.1007/s10072-018-3681-y
- Valproic acid
- Genetic polymorphisms
- Drug-resistant epilepsy
- Focal seizures