Effects of SCN1A and SCN2A polymorphisms on responsiveness to valproic acid monotherapy in epileptic children

Epilepsy Res. 2020 Dec:168:106485. doi: 10.1016/j.eplepsyres.2020.106485. Epub 2020 Oct 11.

Abstract

Purpose: This study was conducted to explore the influence of genetic variations on responsiveness to valproic acid (VPA) monotherapy among Chinese children with epilepsy.

Methods: One hundred and forty epileptic children taking VPA as monotherapy were enrolled, and at least one-year follow-up was obtained to assess the therapeutic outcome. Twenty-seven single nucleotide polymorphisms (SNPs) within twelve candidate genes correlated with the metabolic enzymes, transporters and targets of VPA were genotyped. The effects of selected polymorphisms on VPA efficacy were identified by binary logistic regression analysis adjusting for potential confounders.

Results: SCN2A rs2304016 (A > G) AG genotype was more common among the VPA-resistant patients in comparison with the VPA-responsive patients (OR = 3.18, 95 % CI = 1.10-9.14, P = 0.032), and in subgroup of focal seizure, lower frequency of VPA resistance was found in epileptic children with SCN1A rs2298771 AG genotype than those with AA genotype (OR = 0.11, 95 % CI = 0.01-0.91, P = 0.040).

Conclusions: Our study indicated that SCN2A rs2304016 and SCN1A rs2298771 polymorphisms might be associated with the response to VPA monotherapy in Chinese epileptic children. Further and larger researches are required to validate these results.

Keywords: Epileptic children; Pharmacogenetics; Therapeutic responsiveness; Valproic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticonvulsants / therapeutic use
  • Child
  • Child, Preschool
  • Epilepsy / drug therapy*
  • Epilepsy / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • NAV1.1 Voltage-Gated Sodium Channel / genetics*
  • NAV1.2 Voltage-Gated Sodium Channel / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Seizures / drug therapy
  • Seizures / genetics
  • Valproic Acid / therapeutic use

Substances

  • Anticonvulsants
  • NAV1.1 Voltage-Gated Sodium Channel
  • NAV1.2 Voltage-Gated Sodium Channel
  • SCN1A protein, human
  • SCN2A protein, human
  • Valproic Acid