title: Genetic determinants of warfarin dosing in the Han-Chinese population.
abstract: Warfarin, a widely prescribed oral anticoagulant, is used for the prevention of thromboembolism. Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements. However, it is likely that other genes could also affect warfarin dose.
  
  
  OBJECTIVE
  In this study, we aimed to identify additional genes influencing warfarin dosing in the Han-Chinese population.
  
  
  METHODS
  In this study, we screened for SNPs in 13 genes (VKORC1, CYP2C9, CYP2C18, PROC, APOE, EPHX1, CALU, GGCX, ORM1, ORM2, factor II, factor VII and CYP4F2) and tested their associations with warfarin dosing with univariate and multiple regression analysis.
  
  
  RESULTS
  Polymorphisms in the VKORC1 gene have the strongest effects on warfarin dose, followed by CYP2C9*3. In addition, our results showed that CYP2C18, PROC and EPHX1 have small but significant associations with warfarin dose. In multiple regression analysis, PROC and EPHX1 explained 3% of the dose variation. The incorporation of these two genes into warfarin dosing algorithms could improve the accuracy of prediction in the Han-Chinese population.
authors: Institute of Biomedical Sciences, Academia Sinica, 128, Academia Road, Section 2, NanKang, Taipei, Taiwan.
authors: M T Michael
authors: MT
authors: Lee
authors: Chien-Hsiun
authors: CH
authors: Chen
authors: Ching-Heng
authors: CH
authors: Chou
authors: Liang-Suei
authors: LS
authors: Lu
authors: Hui-Ping
authors: HP
authors: Chuang
authors: Ying-Ting
authors: YT
authors: Chen
authors: Amir N
authors: AN
authors: Saleem
authors: Ming-Shien
authors: MS
authors: Wen
authors: Jin-Jer
authors: JJ
authors: Chen
authors: Jer-Yuarn
authors: JY
authors: Wu
authors: Yuan-Tsong
authors: YT
authors: Chen
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D004305:Dose-Response Relationship, Drug; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008657:Metabolic Clearance Rate / Q000235:genetics; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases