SCN1A Polymorphisms and Haplotypes Are Associated With Valproic Acid Treatment Outcomes in Chinese Children With Epilepsy - 03/08/23
, Xiaomei Fan, PhD a, ⁎ Abstract |
Background |
Sodium channel genes, especially SCN1A, were reported to play an important role in the treatment outcomes of antiseizure medications. The aim of this study was to explore the association of SCN1A polymorphisms with efficacy and adverse drug reactions (ADRs) related to valproic acid (VPA) among Chinese children with epilepsy.
Methods |
A total of 126 children with epilepsy treated with VPA for at least 12 months were enrolled in this study. Three single nucleotide polymorphisms (SNPs) of SCN1A including rs2298771, rs10167228, and rs3812718 were genotyped using Sequenom MassArray system. Bioinformatics tools were used to explore the potential targets and pathways of SCN1A in VPA-related ADRs.
Results |
The three SNPs in this study were found to be closely associated with treatment outcomes for VPA. Carriers of SCN1A rs3812718 TT genotype tended to be seizure-free with VPA treatment (P = 0.007). AA genotype of rs10167228 and TT genotype of rs2298771 might be protective factors for weight gain induced by VPA, whereas TA genotype of rs10167228 and CT genotype of rs2298771 increased the risk. TAT haplotype carriers were found to respond better to VPA treatment (P = 0.017), whereas CTC haplotype might be a risk factor for VPA-induced weight gain (P = 0.035). Bioinformatics analysis suggested that SCN1A might play a role in VPA-induced weight gain by regulating gated channel activity and GABAergic synapse pathway.
Conclusion |
This study revealed that SCN1A rs2298771, rs10167228, and rs3812718 polymorphisms and haplotypes might affect the treatment outcomes of VPA in Chinese children with epilepsy.
Le texte complet de cet article est disponible en PDF.Keywords : Adverse drug reaction, Childhood epilepsy, Polymorphism, Responsiveness, SCN1A, Valproic acid
Plan
| Funding: This study was supported by the National Natural Science Foundation of China (Grant 81603185), the Natural Science Foundation of Guangdong province (Grant 2020A1515011452), the Research Foundation of Shenzhen Baoan Women's and Children's Hospital, Jinan University (BAFY2023001), and the Shenzhen Baoan Medical Health Research Project (Grant 2022JD110). |
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| Data availability statement: The data that support the findings of this study are available from the corresponding author (Dr. Xiaomei Fan) upon reasonable request. |
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| Author Contributions: J.Z., J.L., and X.F. conceived and designed the study. J.Z., J.L., X.S., Y.H., H.X., W.L., and H.G. contributed to the data collection and analysis. J.Z. and J.L. contributed to drafting and writing the manuscript. J.Z. and X.F. reviewed and revised the manuscript. All authors revised it critically for important intellectual content, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work. |
Vol 146
P. 55-64 - septembre 2023 Retour au numéro
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