title: Combined effects of hepatocyte nuclear factor 4α and constitutive androstane receptor on stable warfarin doses.
abstract: A possible association between the combination of genetic variations in hepatocyte nuclear factor 4α (HNF4α) and constitutive androstane receptor (CAR) and the stable doses of warfarin was examined in patients from the Ewha-Severance Treatment (EAST) Group of Warfarin. Around 42.5% of the overall interindividual variability in warfarin dose requirements was explained by the multivariate regression model; the vitamin K epoxide reductase complex 1 (VKORC1) genotype accounted for 29.6%, the cytochrome P450 (CYP) 2C9 genotype for 4.3%, age for 3.6%, the CYP4F2 genotype for 3.3%, and CAR/HNF4α (rs2501873/rs3212198) for 1.7%. Our results showed that the combination of CAR and HNF4α genotypes could be determinants of stable warfarin doses.
authors.affiliation: aDivision of Life and Pharmaceutical Sciences & College of Pharmacy, Ewha Womans University bDepartment of Thoracic & Cardiovascular Surgery, Yonsei University Medical Center, Seoul cCollege of Pharmacy, Chungbuk National University, Chungbuk, Korea.
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Moon
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Chang
authors.forename: Eurim
authors.initials: E
authors.lastname: Jeong
authors.forename: Hotcherl
authors.initials: H
authors.lastname: Jeong
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Gwak
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological; D000090702:Constitutive Androstane Receptor; 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; D019918:Heart Valve Prosthesis Implantation; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D054316:Biomarkers, Pharmacological; D000090702:Constitutive Androstane Receptor; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D018160:Receptors, Cytoplasmic and Nuclear; 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