title: Genetic polymorphisms are associated with variations in warfarin maintenance dose in Han Chinese patients with venous thromboembolism.
abstract: OBJECTIVE
  Warfarin is a clinical anticoagulant that requires periodic monitoring because it is associated with adverse outcomes. Personalized medicine, which is based on pharmacogenetics, holds great promise in solving these types of problems. It aims to provide the tools and knowledge to tailor drug therapy to an individual patient, with the potential of increasing safety and efficacy of medications.
  
  
  METHODS
  In the present study we analyzed genotypes of 14 SNPs for seven genes using DNA from 297 Han Chinese venous thromboembolism patients treated with warfarin.
  
  
  RESULTS
  Multiple regression analyses revealed that CYP2C9 genotype (p = 0.001), VKORC1 genotype (p < 0.001), age (p < 0.01) and weight (p < 0.001) were all associated with warfarin dose requirements, which can explain 37.4% of the variability of warfarin dose among Han Chinese patients. Meanwhile, in the validation cohort, the predicted warfarin daily dose was calculated using the best model with a 64.5% predicted dose being acceptable (-1 mg/day ≤Δwarfarin dose ≤1 mg/day).
  
  
  CONCLUSIONS
  We developed a pharmacogenetic dose algorithm for warfarin treatment that uses genotypes from two genes (VKORC1 and CYP2C9) and clinical variables to predict therapeutic maintenance doses in Chinese patients with venous thromboembolism. The validity of the dosing algorithm was confirmed in a cohort of venous thromboembolism patients on warfarin therapy.
authors.affiliation: Beijing Xiaotangshan Hospital, Xiaotangshan Town, Changping District, Beijing 102211, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Wei-Juan
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.forename: Fan-Cui
authors.initials: FC
authors.lastname: Kong
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Li
authors.forename: He-Yao
authors.initials: HY
authors.lastname: Wang
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Yang
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
mesh_terms: D000367:Age Factors; D000925:Anticoagulants / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D001835:Body Weight / Q000235:genetics; D015331:Cohort Studies; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D010597:Pharmacogenetics / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D054556:Venous Thromboembolism / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; 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