The effect of genetic polymorphisms of cytochrome P450 CYP2C9, CYP2C19, and CYP2D6 on drug-resistant epilepsy in Turkish children

Mol Diagn Ther. 2014 Apr;18(2):229-36. doi: 10.1007/s40291-013-0078-8.

Abstract

Background and objective: Despite the availability of several antiepileptic drugs, drug resistance remains one of the major challenges in epilepsy therapy. Genetic factors are known to play a significant role in the prognosis and treatment of epilepsy. The aim of this study was to determine the frequencies of alleles for CYP2C9, CYP2C19, and CYP2D6 genes in Turkish children with epilepsy, and to investigate the relationship between the genetic polymorphism of these genes with multiple drug resistance in epilepsy patients.

Methods: We genotyped 132 epileptic patients (60 drug resistant and 72 drug responsive) and 55 healthy controls for six single nucleotide polymorphisms (SNPs) in CYP2C9, CYP2C19, and CYP2D6. Genotype, allele, and haplotype frequencies were compared between groups.

Results: The frequencies of CYP2C9*3/*3 genotype and CYP2C9*3 allele, and the haplotype CCGG (CYP2C9*2 C>T, CYP2C9*3 A>C, and CYP2C19*2 G>A, CYP2C19* G>A) were significantly higher in drug-resistant versus -responsive patients.

Conclusion: Our results demonstrated the important role of the CYP2C9*3 allelic variant in preventing epilepsy patients from developing drug resistance. These data suggest that CYP2C9, CYP2C19, and CYP2D6 SNPs and haplotypes may affect the response to antiepileptic drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anticonvulsants / adverse effects*
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 CYP2D6 / genetics*
  • Drug Resistance, Multiple*
  • Epilepsy / drug therapy
  • Epilepsy / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Variation
  • Humans
  • Infant
  • Male
  • Polymorphism, Single Nucleotide*
  • Turkey

Substances

  • Anticonvulsants
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2D6