title: Identification and characterization of a novel CYP2C9 allelic variant in a warfarin-sensitive patient.
abstract: OBJECTIVE
  To determine the genetic basis of the low warfarin dose requirement in a Chinese patient.
  
  
  METHODS
  Bi-directional sequencing of CYP2C9, VKORC1 and CYP4F2 genes was performed. CYP2C9 variants were highly expressed in yeast and insect-cell microsomes. Three typical CYP2C9 probe drugs were used to evaluate the catalytic activity.
  
  
  RESULTS
  A novel missense mutation (1400 T>C) was identified in CYP2C9 and had been named as new allele *60. When expressed in yeast and insect cells, compared with wild-type enzyme, variant CYP2C9.60 exhibited lower protein expression capacity and showed significantly decreased metabolic activities for the hydroxylation of S-warfarin, tolbutamide and diclofenac.
  
  
  CONCLUSIONS
  The novel mutation can greatly decrease the enzymatic activity of the CYP2C9 enzyme both in vitro and in vivo.
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China.
authors.forename: Da-Peng
authors.initials: DP
authors.lastname: Dai
authors.affiliation: The Clinical Laboratory of Beijing Hospital, Ministry of Health, Beijing 100730, China.
authors.forename: Chuan-Bao
authors.initials: CB
authors.lastname: Li
authors.affiliation: The Laboratory of Clinical Pharmacy, the People's Hospital of Lishui, Lishui, Zhejiang 323000, China.
authors.forename: Shuang-Hu
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.affiliation: The Laboratory of Clinical Pharmacy, the People's Hospital of Lishui, Lishui, Zhejiang 323000, China.
authors.forename: Pei-Wu
authors.initials: PW
authors.lastname: Geng
authors.affiliation: The Laboratory of Clinical Pharmacy, the People's Hospital of Lishui, Lishui, Zhejiang 323000, China.
authors.forename: Yun-Fang
authors.initials: YF
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Guo-Xin
authors.initials: GX
authors.lastname: Hu
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Cai
mesh_terms: D000483:Alleles; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044466:Asian People; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007313:Insecta; D019934:International Normalized Ratio; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008875:Middle Aged; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D014859:Warfarin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9
keywords: CYP2C9; allelic variants; drug metabolism; in vitro functional assessment