title: Variability of warfarin dose response associated with CYP2C9 and VKORC1 gene polymorphisms in Chinese patients.
abstract: OBJECTIVE
  To investigate the prevalence and implication of cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) variants and vitamin K epoxide reductase complex, subunit 1 (VKORC1)-1639 G > A polymorphisms in Chinese patients receiving warfarin therapy.
  
  
  METHODS
  Chinese Han patients requiring oral warfarin therapy were consecutively enrolled. Correlations between CYP2C9*1, *2, *3, *4, *5 variants and VKORC1-1639 G > A polymorphisms, fourth-day international normalized ratios (INRs) and warfarin maintenance dose were investigated.
  
  
  RESULTS
  Out of 101 patients, there were no significant differences in fourth-day INR or warfarin daily maintenance doses between patients with CYP2C9*1*1 and CYP2C9*1*3 genotypes. Patients with the VKORC1-1639 AA genotype had a higher fourth-day INR (1.87 ± 0.14) than those with the VKORC1-1639 AG genotype (1.32 ± 0.15). Warfarin maintenance dose for patients with the VKORC1-1639 AA genotype (2.40 ± 0.70 mg/day) was significantly lower than for patients with the VKORC1-1639 AG genotype (4.83 ± 0.70 mg/day).
  
  
  CONCLUSIONS
  Unlike Caucasian populations, VKORC1-1639 G > A polymorphisms in the Chinese population may be the dominant genetic factors associated with warfarin response variability.
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Ye
authors.forename: Haiqiang
authors.initials: H
authors.lastname: Jin
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Yongan
authors.initials: Y
authors.lastname: Sun
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.forename: Weiping
authors.initials: W
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Qing
authors.initials: Q
authors.lastname: Peng
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.forename: Yining
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001483:Base Sequence; D002681:China; D065729:Cytochrome P-450 CYP2C9; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D005006:Ethnicity; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D017931:DNA Primers; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: Warfarin; cytochrome P450; family 2; international normalized ratio (INR); polypeptide 9 (CYP2C9); single nucleotide polymorphism; subfamily C; subunit 1 (VKORC1); vitamin K epoxide reductase complex