SCN1A, ABCC2 and UGT2B7 gene polymorphisms in association with individualized oxcarbazepine therapy

Pharmacogenomics. 2015;16(4):347-60. doi: 10.2217/pgs.14.186.

Abstract

Aim: Associations between the effects of SCN1A, SCN2A, ABCC2 and UGT2B7 genetic polymorphisms and oxcarbazepine (OXC) maintenance doses in Han Chinese epileptic patients were investigated.

Patients & methods: Genetic polymorphisms were detected in 184 epileptic patients receiving OXC monotherapy by high-resolution melting curve and TaqMan method.

Results: Carriers of the SCN1A IVS5-91G>A, UGT2B7 c.802T>C and ABCC2 c.1249G>A variant alleles required significantly higher OXC maintenance doses than noncarriers (p < 0.05). Corresponding relative ln (concentration-dose ratios) values for SCN1A IVS5-91 variants differed by the genotypic order GG > GA > AA.

Conclusion: SCN1A, UGT2B7 and ABCC2 genetic polymorphisms are associated with OXC maintenance doses and may be useful for the personalization of OXC therapy in epileptic patients. Further studies are needed. Original submitted 6 June 2014; Revision submitted 5 September 2014.

Keywords: ABCC2; SCN1A; SCN2A; UGT2B7; epilepsy; genetic polymorphisms; oxcarbazepine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / adverse effects
  • Carbamazepine / administration & dosage
  • Carbamazepine / adverse effects
  • Carbamazepine / analogs & derivatives
  • Dose-Response Relationship, Drug
  • Epilepsy / drug therapy*
  • Epilepsy / genetics
  • Epilepsy / pathology
  • Female
  • Genetic Association Studies
  • Genotype
  • Glucuronosyltransferase / genetics*
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins / genetics*
  • NAV1.1 Voltage-Gated Sodium Channel / genetics*
  • Oxcarbazepine
  • Polymorphism, Single Nucleotide

Substances

  • ABCC2 protein, human
  • Anticonvulsants
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • NAV1.1 Voltage-Gated Sodium Channel
  • SCN1A protein, human
  • Carbamazepine
  • UGT2B7 protein, human
  • Glucuronosyltransferase
  • Oxcarbazepine