title: Contribution of 1173C > T polymorphism in the VKORC1 gene to warfarin dose requirements in Han Chinese patients receiving anticoagulation.
abstract: OBJECTIVE
  The objective was to assess 1173C > T polymorphism of the VKORC1 gene and its contribution to warfarin dose requirements in Han Chinese patients.
  
  
  METHODS
  Blood samples were collected from 178 patients with stable warfarin dose requirements and an international normalized ratio (INR) of the prothrombin time within the target range (1.5 - 3.0). Polymorphisms for VKORC1 (1173C > T), CYP2C9, venous INR, and plasma concentration and unbound concentration of warfarin were analyzed.
  
  
  RESULTS
  VKORC1 (1173C > T) genotyping showed that 154 patients were homozygous TT, 23 were heterozygous CT, and one was homozygous for the CC genotype. Patients with the VKORC1 (1173CC + CT) genotype required a significantly higher warfarin dose (3.33 ± 1.04 mg/day) than those with 1173TT (1.81 ± 0.63 mg/day; p < 0.001). The multiple linear regression model for warfarin dose indicated significant contributions from the VKORC1 (1173C > T) genotype (r2 = 0.355; p < 0.001), and age, body weight, and CYP2C9 and VKORC1 genotype together (r2 = 0.513; p < 0.001). The two SNPs (-1639 and 1173) were found to be in very strong linkage disequilibrium with estimated D' = 0.96 (95%CI (0.83 - 0.99)).
  
  
  CONCLUSIONS
  The VKORC1 (1173C > T) polymorphism might be very important, and its contribution can be equally explained by the VKORC1(-1639 G > A) polymorphism for warfarin dose requirements in Han Chinese patients.
authors.affiliation: Institute of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: C
authors.initials: C
authors.lastname: Huang
authors.forename: Z
authors.initials: Z
authors.lastname: Shen
authors.forename: L
authors.initials: L
authors.lastname: Miao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D002681:China / Q000208:ethnology; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases