title: Influence of genetic, biological and pharmacological factors on warfarin dose in a Southern Brazilian population of European ancestry.
abstract: OBJECTIVE
  To investigate the influence of polymorphisms in CYP2C9, VKORC1, CYP4F2 and F2 genes on warfarin dose-response and develop a model including genetic and non-genetic factors for warfarin dose prediction needed for each patient.
  
  
  METHODS
  A total of 279 patients of European ancestry on warfarin medication were investigated. Genotypes for -1639G>A, 1173C>T, and 3730G>A SNPs in the VKORC1 gene, CYP2C9*2 and CYP2C9*3, 1347C>T in the CYP4F2 gene and 494C>T in the F2 gene were determined by allelic discrimination with Taqman 5'-nuclease assays.
  
  
  RESULTS
  The CYP2C9*2 and CYP2C9*3 polymorphisms in the CYP2C9 gene, -1639G>A and 1173C>T in the VKORC1 gene and 494C>T in the F2 gene are responsible for lower anticoagulant doses. In contrast, 1347C>T in the CYP4F2 gene and 3730G>A in the VKORC1 gene are responsible for higher doses of warfarin. An algorithm including genetic, biological and pharmacological factors that explains 63.3% of warfarin dose variation was developed.
  
  
  CONCLUSIONS
  The model suggested has one of the highest coefficients of determination among those described in the literature.
authors.affiliation: Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Mariana Rodrigues
authors.initials: MR
authors.lastname: Botton
authors.forename: Eliane
authors.initials: E
authors.lastname: Bandinelli
authors.forename: Luis Eduardo Paim
authors.initials: LE
authors.lastname: Rohde
authors.forename: Luis Carlos
authors.initials: LC
authors.lastname: Amon
authors.forename: Mara Helena
authors.initials: MH
authors.lastname: Hutz
mesh_terms: D000368:Aged; D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001938:Brazil / Q000453:epidemiology; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D013223:Statistics as Topic; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage*; D044465:White People / Q000235:genetics*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases