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  • Title: CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability in patients on long-term anticoagulation.
    Author: Santos PC, Dinardo CL, Schettert IT, Soares RA, Kawabata-Yoshihara L, Bensenor IM, Krieger JE, Lotufo PA, Pereira AC.
    Journal: Eur J Clin Pharmacol; 2013 Apr; 69(4):789-97. PubMed ID: 22990331.
    Abstract:
    OBJECTIVES: The main aim of this study was to determine whether CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability during initial dose-finding phase and during maintenance treatment after 360 days. METHODS: Two hundred and six consecutive patients who were beginning warfarin therapy were selected. They were assessed for general and clinical characteristics; prescribed warfarin dose; response to therapy on days 7-10, 30, 60, 180, and 360; adverse events; and CYP2C9 2, 3, 5, 6, 8, 11, and VKORC1 1639G >A assays. RESULTS: During the first 30 days of anticoagulation, the relative variability of warfarin dose was significantly associated with CYP2C9*2 and CYP2C9*3 polymorphisms (p = 0.02) and with VKORC1 1639G >A genotypes (p = 0.04). Warfarin variability was also statistically different according to predicted metabolic phenotype and to VKORC1 genotypes after 360 days of treatment, and in the phase between 180 and 360 days (long-term dose variability). Both CYP2C9 and VKORC1 polymorphisms were associated with the international normalized ratio (INR) made between 7 and 10 days/initial dose ratio, adjusted for covariates (p < 0.01 and p = 0.02, respectively). Patients carrying VKORC1 and CYP2C9 variants presented lower required dose (at the end of follow-up of 360 days) compared to patients carrying wild-type genotypes (p = 0.04 and p = 0.03, respectively). CONCLUSIONS: Genetic information on CYP2C9 and VKORC1 is important both for the initial dose-finding phase and during maintenance treatment with warfarin.
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