title: Possible role of CYP2C9 & CYP2C19 single nucleotide polymorphisms in drug refractory epilepsy.
abstract: OBJECTIVE
  Multiple drug resistance in epilepsy is a common problem and one third of epilepsy patients remain non responsive to antiepileptic drug (AED) therapy. In this study we aimed to investigate the relationship between the genetic polymorphism of cytochrome P450 genes, namely CYP2C9 and CYP2C19 with multiple drug resistance in epilepsy patients.
  
  
  METHODS
  A total of 402 patients with epilepsy were enrolled in this study; 128 were drug resistant and 274 were drug responsive. The peripheral blood samples of the patients with epilepsy were collected. Drug compliance was confirmed in 20 per cent patient population using HPLC. Genotyping of CYP2C9 (FNx012 and FNx013), and CYP2C19 (FNx012 andFNx013) was carried out by PCR-RFLP.
  
  
  RESULTS
  The genotype frequencies of CYP2C9 430 C>T (FNx012 variant) and CYP2C9 1075 A>C (FNx013 variant) did not differ significantly in drug resistant versus responsive patients. After combining CYP2C9 FNx012 and CYP2C9 FNx013, the frequency of CYP2C9FNx011/FNx013 was significantly lower in drug resistant as compared to drug responsive epilepsy patients (P=0.03, OR=0.53, 95%CI=0.30-0.95). Similarly, combined frequency of all the slow and poor metabolizer variants (2C9 FNx011/FNx012, FNx011/FNx013 and FNx012/FNx013) was also lower as compared to drug resistant group (P=0.03, OR=0.60, 95% CI 0.38-0.96). There was no significant differences in genotypic or allelic distribution of CYP2C190FNx012 while CYP2C19FNx013 was monomorphic in northern Indian population.
  
  
  CONCLUSIONS
  Our results demonstrated significant involvement of CYP2C9 genetic variants in the modulation of epilepsy pharmacotherapy confirming the important role of CYP2C9 mutants preventing epilepsy patients from developing drug resistance.
authors: Department of Genetics, Sanjay Gandhi Postgraduate, Institute of Medical Sciences, Lucknow, India.
authors: Ram
authors: R
authors: Lakhan
authors: Ritu
authors: R
authors: Kumari
authors: Kavita
authors: K
authors: Singh
authors: Jayanti
authors: J
authors: Kalita
authors: Usha Kant
authors: UK
authors: Misra
authors: Balraj
authors: B
authors: Mittal
mesh_terms: D000293:Adolescent; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D017931:DNA Primers / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007194:India; D008297:Male; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D017931:DNA Primers; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19