title: Effects of major transporter and metabolizing enzyme gene polymorphisms on carbamazepine metabolism in Chinese patients with epilepsy.
abstract: OBJECTIVE
  The present study aimed to evaluate the effects of SNPs of major transporter and metabolizing enzyme genes on carbamazepine (CBZ) metabolism in Chinese patients with epilepsy.
  
  
  METHODS
  For 210 epileptic patients treated with CBZ as monotherapy, nine SNPs in candidate genes ABCB1, CYP3A4, CYP3A5, POR and EPHX1 were analyzed by PCR-RFLP or direct sequencing. Serum concentrations of CBZ, carbamazepine-10,11-epoxide (CBZE) and carbamazepine-10,11-trans dihydrodiol (CBZD) were determined by HPLC. Dose-adjusted concentrations of CBZ (CDRCBZ), CBZE (CDRCBZE), CBZD (CDRCBZ D) and CBZD:CBZE ratio were used as evaluation parameters for CBZ metabolism.
  
  
  RESULTS
  The ABCB1 c.3435C>T was significantly associated with the CDR of CBZ and its major metabolites. CYP3A4*1G and CYP3A5*3 could influence CBZ metabolism, while POR*28 had no effect on it. The EPHX1 c.416A>G and c.128G>C variants were significantly associated with CBZD:CBZE ratio.
  
  
  CONCLUSIONS
  Our data suggest that certain polymorphisms of major transporter and metabolizing enzyme genes could in part influence interindividual variability of CBZ metabolism in Chinese patients with epilepsy.
authors.affiliation: Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhu
authors.forename: Wenting
authors.initials: W
authors.lastname: Yun
authors.forename: Xiaofu
authors.initials: X
authors.lastname: Sun
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
authors.forename: Limei
authors.initials: L
authors.lastname: Zhao
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Guo
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D002220:Carbamazepine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; C101158:ARFIP2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D048868:Adaptor Proteins, Signal Transducing; D002220:Carbamazepine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human
keywords: ABCB1; CYP3A4; CYP3A5; EPHX1; POR; carbamazepine; metabolism; polymorphism