title: Effect of the VKORC1 genotype on warfarin dose requirements in Japanese pediatric patients.
abstract: The primary aim of the present study was to evaluate the effect of the genotype of vitamin K epoxide reductase complex 1 (VKORC1) on warfarin dose requirements in Japanese pediatric patients. Forty-eight pediatric patients (0.42-19.25 years old) in whom stable anticoagulation was achieved by warfarin were enrolled in this study, and the polymorphic alleles of VKORC1 and CYP2C9 were determined for each subject. The relative impact of covariates on the anticoagulant effect of warfarin was evaluated by multiple regression analysis. It was found that VKORC1 genotype and age were major factors affecting the relationship between the weight-normalized warfarin dose and the therapeutic prothrombin time-international normalized ratio (PT-INR). Because only one patient had the CYP2C9*3 allele, we could not evaluate the effect of CYP2C9 polymorphisms on the anticoagulant effect of warfarin. In contrast, the anticoagulant effect of warfarin in patients with the VKORC1 1173CT or 1173CC genotype was 52.3% of that in patients with the 1173TT genotype. In addition, the anticoagulant effect of warfarin was shown to increase by 10.5% per year in Japanese pediatric patients. In conclusion, genotyping of VKORC1 will be useful in establishing individual anticoagulant therapy with warfarin, and it should be noted that a higher weight-normalized dose of warfarin is required in younger pediatric patients.
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kato
authors.forename: Fukiko
authors.initials: F
authors.lastname: Ichida
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Saito
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Watanabe
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hirono
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyawaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Isao
authors.initials: I
authors.lastname: Horiuchi
authors.forename: Masato
authors.initials: M
authors.lastname: Taguchi
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D001835:Body Weight / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D065729:Cytochrome P-450 CYP2C9; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D005838:Genotype; D006330:Heart Defects, Congenital / Q000601:surgery; D006801:Humans; D007223:Infant; D016013:Likelihood Functions; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D008954:Models, Biological; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011517:Prothrombin Time; D012044:Regression Analysis; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
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