title: Effects of polymorphisms in six candidate genes on phenytoin maintenance therapy in Han Chinese patients.
abstract: OBJECTIVE
  The present study aimed to investigate the associations between variants in pharmacokinetic- and pharmacodynamic-related genes with the dosages, concentrations and concentration-dose ratios (CDRs) of phenytoin (PHT).
  
  
  RESULTS
  Eleven genetic polymorphisms in the six candidate genes were detected in 269 epileptic patients under maintenance PHT monotherapy by real-time PCR and PCR-RFLP. Results of a bivariate analysis demonstrated that among tested polymorphisms, carriers of the variant CYP2C9*3 tended to require significantly lower maintenance PHT dosages than wild-type carriers (p < 0.0001); on the other hand, carriers of the variants CYP2C9*3 or CYP2C19*3 revealed significantly higher CDRs than wild-type carriers (p < 0.004). In a further multivariate analysis, variants in SCN1A, CYP2C9, CYP2C19 and ABCB1 genes were significantly associated with CDRs of PHT under adjustment of age, gender and epilepsy classifications (adjusted r(2) = 20.07%).
  
  
  CONCLUSIONS
  The results of present study indicated that polygenic analysis may provide useful information in PHT therapy optimization.
authors.affiliation: Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Chin-Chuan
authors.initials: CC
authors.lastname: Hung
authors.forename: Hsiao-Ching
authors.initials: HC
authors.lastname: Huang
authors.forename: Yun-Han
authors.initials: YH
authors.lastname: Gao
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Chang
authors.forename: Jia-Ling
authors.initials: JL
authors.lastname: Ho
authors.forename: Mu-Han
authors.initials: MH
authors.lastname: Chiou
authors.forename: Yow-Wen
authors.initials: YW
authors.lastname: Hsieh
authors.forename: Horng-Huei
authors.initials: HH
authors.lastname: Liou
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D000483:Alleles; D000927:Anticonvulsants / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D044466:Asian People / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010672:Phenytoin / Q000008:administration & dosage*; D011110:Polymorphism, Genetic
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D010672:Phenytoin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19