title: [Impact of five genetic polymorphisms on inter-individual variation in warfarin maintenance dose].
abstract: OBJECTIVE
  To investigate the effect of genetic polymorphisms in VKORC1, CYP2C9, GGCX, EPHX1, APOE genes on inter-individual variation in warfarin maintenance dose.
  
  
  METHODS
  Two hundred and forty-nine patients with stable warfarin dose were enrolled in this study, and the clinical data and blood samples of the patients were collected. Genotypes for the 5 genes were determined by using PCR and denaturing high performance liquid chromatography (DHPLC) assay. The warfarin maintenance doses were compared among patients with different genotypes of the 5 genes, and a warfarin stable dosing algorithm was derived based on genetic and non-genetic factors.
  
  
  RESULTS
  Of the 5 genes, VKORC1, CYP2C9 and GGCX were associated with warfarin stable dose. The multiple linear regression analysis indicated that  VKORC1, CYP2C9 and GGCX genes, age and weight,  had significant influence on inter-individual variation in warfarin stable dose, which contributed 30.2%, 22.8%, 1.5%, 4.7% and 6.7% respectively. The warfarin stable dosing algorithm acquired from the optimal regression model could explain 57.8% variation in warfarin dose.
  
  
  CONCLUSIONS
  This study suggested that genetic factors are the major determinants of the warfarin maintenance dose, and warfarin stable dosing algorithm may be useful for helping clinicians to prescribe warfarin with greater safety and efficiency.
authors.affiliation: Department of Laboratory Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou, People's Republic of China. hsw713@sina.com
authors.forename: Sheng-wen
authors.initials: SW
authors.lastname: Huang
authors.forename: Dao-kang
authors.initials: DK
authors.lastname: Xiang
authors.forename: Hai-li
authors.initials: HL
authors.lastname: Wu
authors.forename: Bao-lin
authors.initials: BL
authors.lastname: Chen
authors.forename: Bang-quan
authors.initials: BQ
authors.lastname: An
authors.forename: Gui-fang
authors.initials: GF
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000925:Anticoagulants / Q000008:administration & dosage*; D001057:Apolipoproteins E / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D019735:Carbon-Carbon Ligases / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D001057:Apolipoproteins E; 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; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase