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https://observatorio.fm.usp.br/handle/OPI/1734
Title: | CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability in patients on long-term anticoagulation |
Authors: | SANTOS, Paulo Caleb Junior Lima; DINARDO, Carla Luana; SCHETTERT, Isolmar Tadeu; SOARES, Renata Alonso Gadi; KAWABATA-YOSHIHARA, Liz; BENSENOR, Isabela Martins; KRIEGER, Jose Eduardo; LOTUFO, Paulo Andrade; PEREIRA, Alexandre Costa |
Citation: | EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, v.69, n.4, p.789-797, 2013 |
Abstract: | 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. 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. 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). Genetic information on CYP2C9 and VKORC1 is important both for the initial dose-finding phase and during maintenance treatment with warfarin. |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - FM/MCM Artigos e Materiais de Revistas Científicas - FM/MCP Artigos e Materiais de Revistas Científicas - HC/ICHC Artigos e Materiais de Revistas Científicas - HC/InCor Artigos e Materiais de Revistas Científicas - HU Artigos e Materiais de Revistas Científicas - LIM/13 |
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