title: CYP2C9 polymorphism in patients with epilepsy: genotypic frequency analyzes and phenytoin adverse reactions correlation.
abstract: OBJECTIVE
  CYP2C9 is a major enzyme in human drug metabolism and the polymorphism observed in the corresponding gene may affect therapeutic outcome during treatment. The distribution of variant CYP2C9 alleles and prevalence of phenytoin adverse reactions were hereby investigated in a population of patients diagnosed with epilepsy.
  
  
  METHODS
  Allele-specific PCR analysis was carried out in order to determine frequencies of the two most common variant alleles, CYP2C9*2 and CYP2C9*3 in genomic DNA isolated from 100 epileptic patients. We also analyzed the frequency of phenytoin adverse reactions among those different genotypes groups. The data was presented as mean±standard deviation.
  
  
  RESULTS
  The mean age at enrollment was 39.6±10.3 years (range, 17-72 years) and duration of epilepsy was 26.5±11.9 years (range 3-48 years). The mean age at epilepsy onset was 13.1±12.4 years (range, 1 month-62 years). Frequencies of CYP2C9*1 (84%), CYP2C9*2 (9%) and CYP2C9*3 (7%) were similar to other published reports. Phenytoin adverse reactions were usually mild and occurred in 15% patients, without correlation with the CYP2C9 polymorphism (p=0.34).
  
  
  CONCLUSIONS
  Our findings indicate an overall similar distribution of the CYP2C9 alleles in a population of patients diagnosed with epilepsy in the South of Brazil, compared to other samples. This sample of phenytoin users showed no drug related adverse reactions and CYP2C9 allele type correlation. The role of CYP2C9 polymorphism influence on phenytoin adverse reaction remains to be determined since some literature evidence and our data found negative results.
authors.affiliation: Molecular Biology Laboratory, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Carlos Alexandre
authors.initials: CA
authors.lastname: Twardowschy
authors.forename: Lineu César
authors.initials: LC
authors.lastname: Werneck
authors.forename: Rosana Herminia
authors.initials: RH
authors.lastname: Scola
authors.forename: Luciano
authors.initials: L
authors.lastname: De Paola
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Silvado
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000008:administration & dosage / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D010672:Phenytoin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases