Pharmacogenetics of calcineurin inhibitors in Brazilian renal transplant patients

Página do item simplificado
dc.contributor.authorSantoro, Ana
dc.contributor.authorFelipe, Claudia Rosso [UNIFESP]
dc.contributor.authorTedesco-Silva, Helio [UNIFESP]
dc.contributor.authorMedina-Pestana, Jose O. [UNIFESP]
dc.contributor.authorStruchiner, Claudio J.
dc.contributor.authorOjopi, Elida B.
dc.contributor.authorSuarez-Kurtz, Guilherme
dc.contributor.institutionInst Nacl Canc
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionFundacao Oswaldo Cruz
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2016-01-24T14:17:12Z
dc.date.available2016-01-24T14:17:12Z
dc.date.issued2011-09-01
dc.description.abstractAim: Polymorphisms in the CYP3A5 and ABCB1 genes have been investigated as modulators of the pharmacokinetics and clinical effects of cyclosporine (CSA) and tacrolimus (TAC) in European, North American and Asian populations, with controversial results. the extensive variation in worldwide frequency distribution of CYP3A5 and ABCB1 polymorphisms is a caveat against the extrapolation of these data to the heterogeneous and admixed Brazilian population. We investigated the effect of CYP3A5 and ABCB1 polymorphisms on CSA and TAC dose-adjusted trough concentration (C(0)/dose) in Brazilian renal transplant recipients, during the first 3 months post-transplantation. Materials & methods: Patients receiving CSA (n = 150) or TAC (n = 151) were genotyped for CYP3A5(star)3 (rs776746, 6986A>G), (star)6(rs10264272, 14690G>A) and (star) 7 (rs41303343, 27131-27132insT) and for ABCB1 1236C>T (rs1128503), 2677G>T/A (rs2032582) and 3435C>T (rs1045642) polymorphisms. We explored the effects of CYP3A5 and ABCB1 polymorphisms, clinical and demographical characteristics on CSA and TAC C(0)/dose under a two-step data ana-lysis strategy by fitting a longitudinal mixed-effects model to the data; first to select the important covariates under a univariate setting and then to fit the final multivariate model. Results: C(0)/dose of TAC was associated with the number of CYP3A5-defective alleles, in a gene-dose manner, throughout the observation period, whereas C0/dose of CSA was associated with body surface area and prednisone dosing. No other significant associations were detected. Conclusion: Individual adjustment of the initial TAC dose according to the CYP3A5 haplotypes comprising the CYP3A5(star)3, (star)6 and (star)7 defective alleles might prove beneficial to Brazilian renal transplant recipients and should be further investigated in prospective trials. Original submitted 5 April 2011; Revision submitted 4 May 2011en
dc.description.affiliationInst Nacl Canc, Div Farmacol, BR-20231050 Rio de Janeiro, Brazil
dc.description.affiliationHosp Rim & Hipertensao UNIFESP, São Paulo, Brazil
dc.description.affiliationFundacao Oswaldo Cruz, Programa Comp Cient, Rio de Janeiro, Brazil
dc.description.affiliationUniv São Paulo, Fac Med, Inst Psiquiatria, Lab Neurociencias LIM 27, São Paulo, Brazil
dc.description.affiliationUnifespHosp Rim & Hipertensao UNIFESP, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFinanciadora de Estudos e Projetos (Finep)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
dc.description.sponsorshipIDFinanciadora de Estudos e Projetos (Finep): 01.08.01230.00
dc.format.extent1293-1303
dc.identifierhttp://dx.doi.org/10.2217/PGS.11.70
dc.identifier.citationPharmacogenomics. London: Future Medicine Ltd, v. 12, n. 9, p. 1293-1303, 2011.
dc.identifier.doi10.2217/PGS.11.70
dc.identifier.issn1462-2416
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/34039
dc.identifier.wosWOS:000295728800016
dc.language.isoeng
dc.publisherFuture Medicine Ltd
dc.relation.ispartofPharmacogenomics
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectABCB1en
dc.subjectBrazilen
dc.subjectcalcineurin inhibitorsen
dc.subjectcyclosporineen
dc.subjectCYP3A5en
dc.subjectrenal transplanten
dc.subjecttacrolimusen
dc.titlePharmacogenetics of calcineurin inhibitors in Brazilian renal transplant patientsen
dc.typeinfo:eu-repo/semantics/article
Arquivos
Coleções
EPM - Artigos