title: [Influence of warfarin related genes and non- genetic factors on administrative dose in Shanghai area].
abstract: OBJECTIVE
  To investigate the distribution of Warfarin related genes and the relationship between genotype, gender, weight, age and the administrative dose of Warfarin in Shanghai area.
  
  
  METHODS
  The clinical data (including sex, age and administrative dose of Warfarin) of 214 patients with stable warfarin dose and the international normalized ratio (INR) between 1.5-3.0 were collected. Polymerase chain reaction-high resolution melting (PCR-HRM) technique was used to detect the single nucleotide polymorphisms (SNPs) of CYP2C9*2 rs1799853, CYP2C9*3 rs1057910, CYP4F2 rs2108622 and VKORC1 rs9934438. The associations of genotype data with clinical material, including gender, age, weight and warfarin dosage were analyzed.
  
  
  RESULTS
  Among 214 patients, 99.53% (213 cases) patients with CC (wild type) of CYP2C9*2 rs1799853 and only 1 case with CT (heterozygous mutation) ; 92.52% (198 cases) with AA (wild type), 7.48% (16 cases) with CA (heterozygous mutation) of CYP2C9*3rs1057910; about 57.94% (124 cases) with CC(wild type) of CYP4F2 rs2108622, the CT and TT (heterozygous and homozygotic mutation) accounted for 42.06% (90 cases). In SNP VKORC1 rs9934438, 82.71% (177cases) were TT (wild type), 17.29% (37 cases) CT (heterozygous mutation). There are no significant difference (P=0.0872) in patients with maintenance dose in CYP2C9*3 between AA and CA gene mutations[(2.816±1.055) mg/d vs (2.352±0.805)mg/d], and no significant difference (P=0.5954) of that in CYP4F2 between CC and CT+TT gene mutations [(2.736±1.062) mg/d vs (2.813±1.034) mg/d]; but the significant differences (P=0.0001) does exist in patients with maintenance dose in VKORC1 between TT and CT variants [(2.597±0.866) mg/d vs (3.660±1.350) mg/d]. The warfarin maintain dosage was negatively correlated with the average age (r=-0.9669) and positively correlated with the body weight (r=0.9022).
  
  
  CONCLUSIONS
  It is of great significance to detect the VKORC1 variants for warfarin dosage adjustment in Shanghai population. However, the detection of CYP2C9*2 and CYP4F2 polymorphisms had no significant associations for warfarin dosage adjustment.
authors.affiliation: The First Affiliated Hospital of Suzhou University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou 215006, China.
authors.forename: Wenfang
authors.initials: W
authors.lastname: Zhuang
authors.affiliation: The First Affiliated Hospital of Suzhou University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou 215006, China.
authors.forename: Depei
authors.initials: D
authors.lastname: Wu
authors.affiliation: The First Affiliated Hospital of Suzhou University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou 215006, China.
authors.forename: Zhaoyue
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D001835:Body Weight; D002681:China / Q000453:epidemiology; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D017678:Sex Distribution; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases