CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability in patients on long-term anticoagulation

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Arquivos
art_SANTOS_CYP2C9_and_VKORC1_polymorphisms_influence_warfarin_dose_variability_2013.PDF (316.7 KB)
Citações na Scopus
26
Tipo de produção
article
Data de publicação
2013
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
SPRINGER HEIDELBERG
Autores
SOARES, Renata Alonso Gadi
Citação
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, v.69, n.4, p.789-797, 2013
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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.
Palavras-chave
CYP2C9, VKORC1, Warfarin, Anticoagulation, Pharmacogenetic
URI
https://observatorio.fm.usp.br/handle/OPI/1734
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Coleções
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