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

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author SANTOS, Paulo Caleb Junior Lima FMUSP-HC
DINARDO, Carla Luana FMUSP-HC
SCHETTERT, Isolmar Tadeu FMUSP-HC
SOARES, Renata Alonso Gadi
KAWABATA-YOSHIHARA, Liz FMUSP-HC
BENSENOR, Isabela Martins FMUSP-HC
KRIEGER, Jose Eduardo FMUSP-HC
LOTUFO, Paulo Andrade FMUSP-HC
PEREIRA, Alexandre Costa FMUSP-HC
dc.date.issued 2013
dc.identifier.citation EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, v.69, n.4, p.789-797, 2013
dc.identifier.issn 0031-6970
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/1734
dc.description.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.
dc.description.sponsorship · FAPESP, Brazil [Proc. 10-17465-8, Proc. 10-17881-1]
dc.language.iso eng
dc.publisher SPRINGER HEIDELBERG
dc.relation.ispartof European Journal of Clinical Pharmacology
dc.rights restrictedAccess
dc.subject CYP2C9; VKORC1; Warfarin; Anticoagulation; Pharmacogenetic
dc.subject.other international normalized ratio; optimal therapeutic range; chinese patients; clinical effectiveness; arterial stiffness; general-population; african-americans; dosing regimen; requirements; complications
dc.title CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability in patients on long-term anticoagulation
dc.type article
dc.rights.holder Copyright SPRINGER HEIDELBERG
dc.description.group LIM/13
dc.identifier.doi 10.1007/s00228-012-1404-5
dc.identifier.pmid 22990331
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author SANTOS, Paulo Caleb Junior Lima:FM:
hcfmusp.author DINARDO, Carla Luana:FM:
hcfmusp.author SCHETTERT, Isolmar Tadeu:HC:LIM/13
hcfmusp.author KAWABATA-YOSHIHARA, Liz:HU:
hcfmusp.author BENSENOR, Isabela Martins:FM:MCM
hcfmusp.author KRIEGER, Jose Eduardo:FM:MCP
hcfmusp.author LOTUFO, Paulo Andrade:FM:MCM
hcfmusp.author PEREIRA, Alexandre Costa:HC:LIM/13
hcfmusp.author.external · SOARES, Renata Alonso Gadi:Univ Sao Paulo, Sch Med, Lab Genet & Mol Cardiol, Heart Inst InCor, BR-05403000 Sao Paulo, Brazil
hcfmusp.origem.id WOS:000317364100007
hcfmusp.origem.id 2-s2.0-84876743679
hcfmusp.publisher.city HEIDELBERG
hcfmusp.publisher.country GERMANY
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dc.description.index MEDLINE
hcfmusp.citation.scopus 20
hcfmusp.citation.wos 18
hcfmusp.affiliation.country Brasil


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