Association Between ABCB1 Polymorphism and Stable Warfarin Dose Requirements in Brazilian Patients

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dc.contributor.authorTavares, Leticia C.
dc.contributor.authorMarcatto, Leiliane R.
dc.contributor.authorSoares, Renata A. G.
dc.contributor.authorKrieger, Jose Eduardo [UNIFESP]
dc.contributor.authorPereira, Alexandre C.
dc.contributor.authorSantos, Paulo C. J. L. [UNIFESP]
dc.date.accessioned2018-07-26T12:18:46Z
dc.date.available2018-07-26T12:18:46Z
dc.date.issued2018
dc.description.abstractThe ideal dose of the oral anticoagulant warfarin varies widely among patients, mainly due to genetic factors. Genetic variations that impact warfarin pharmacokinetics and the vitamin K cycle are plausible candidates for being associated with warfarin dose requirements. Therefore, the aim of this study was to assess whether polymorphisms in the ABCB1 and CYP4F2 genes were associated with stable warfarin dose requirements in Brazilian patients. This retrospective study included samples from 309 individuals. Genotyping of ABCB1 c.3435C>T and CYP4F2 c.1297G>A were performed by polymerase chain reaction followed by melting curve analysis (HRM-PCR) and TaqMan((R)) genotyping assay, respectively. Stable doses were adjusted in a linear multiple regression model for age, gender, body mass index, self-reported race, use of amiodarone, CYP2C9 (*2 and *3), VKORC1 c.1639G>A, and ABCB1 c.3435C>T or CYP4F2 c.1297G>A. By performing a univariate analysis of variance, we found that the warfarin patients who carry ABCB1 c.3435T variant alleles (CT and TT genotypes) need fewer warfarin stable doses in comparison with the individuals that are CC wild-type: 2.5 (p = 0.003) and 4.3 (p < 0.001) mg/week less, respectively, for the overall group of patients on stable anticoagulation therapeutics (n = 309)en
dc.description.abstractand 5.5 (p = 0.006) and 10.2 (p < 0.001) mg/week less, respectively, for the self-declared non-white stable subgroup ( n = 76). No statistically significant differences in dose requirements were observed according to CYP4F2 genotypes. In conclusion, our results suggest ABCB1 c.3435C>T variant may influence warfarin dose requirements in Brazilian patients, when associated with other genotypic, demographic and clinical factors.en
dc.description.affiliationUniv Sao Paulo, Fac Med FMUSP, Heart Inst InCor, Lab Genet & Mol Cardiol, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo UNIFESP, Dept Pharmacol, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo UNIFESP, Dept Pharmacol, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipSao Paulo Research Foundation (FAPESP)
dc.description.sponsorshipGraduate Program in Medical Sciences-FMUSP
dc.description.sponsorshipIDFAPESP: 2013/09295-3
dc.description.sponsorshipIDFAPESP: 2016/22507-8
dc.description.sponsorshipIDFAPESP: 2016/23454-5
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.3389/fphar.2018.00542
dc.identifier.citationFrontiers In Pharmacology. Lausanne, v. 9, p. -, 2018.
dc.identifier.doi10.3389/fphar.2018.00542
dc.identifier.fileWOS000432812200001.pdf
dc.identifier.issn1663-9812
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/46030
dc.identifier.wosWOS:000432812200001
dc.language.isoeng
dc.publisherFrontiers Media Sa
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectwarfarin pharmacogeneticsen
dc.subjectABCB1en
dc.subjectMDR1en
dc.subjectCYP4F2en
dc.subjectwarfarin stable doseen
dc.titleAssociation Between ABCB1 Polymorphism and Stable Warfarin Dose Requirements in Brazilian Patientsen
dc.typeinfo:eu-repo/semantics/article
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