Pharmacogenetics of calcineurin inhibitors in Brazilian renal transplant patients

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dc.contributor.author Santoro, Ana
dc.contributor.author Felipe, Claudia Rosso [UNIFESP]
dc.contributor.author Tedesco-Silva, Helio [UNIFESP]
dc.contributor.author Medina-Pestana, Jose O. [UNIFESP]
dc.contributor.author Struchiner, Claudio J.
dc.contributor.author Ojopi, Elida B.
dc.contributor.author Suarez-Kurtz, Guilherme
dc.date.accessioned 2016-01-24T14:17:12Z
dc.date.available 2016-01-24T14:17:12Z
dc.date.issued 2011-09-01
dc.identifier http://dx.doi.org/10.2217/PGS.11.70
dc.identifier.citation Pharmacogenomics. London: Future Medicine Ltd, v. 12, n. 9, p. 1293-1303, 2011.
dc.identifier.issn 1462-2416
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/34039
dc.description.abstract Aim: 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 2011 en
dc.description.sponsorship Financiadora de Estudos e Projetos (Finep)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
dc.format.extent 1293-1303
dc.language.iso eng
dc.publisher Future Medicine Ltd
dc.relation.ispartof Pharmacogenomics
dc.rights Acesso restrito
dc.subject ABCB1 en
dc.subject Brazil en
dc.subject calcineurin inhibitors en
dc.subject cyclosporine en
dc.subject CYP3A5 en
dc.subject renal transplant en
dc.subject tacrolimus en
dc.title Pharmacogenetics of calcineurin inhibitors in Brazilian renal transplant patients en
dc.type Artigo
dc.contributor.institution Inst Nacl Canc
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Fundacao Oswaldo Cruz
dc.contributor.institution Universidade de São Paulo (USP)
dc.description.affiliation Inst Nacl Canc, Div Farmacol, BR-20231050 Rio de Janeiro, Brazil
dc.description.affiliation Hosp Rim & Hipertensao UNIFESP, São Paulo, Brazil
dc.description.affiliation Fundacao Oswaldo Cruz, Programa Comp Cient, Rio de Janeiro, Brazil
dc.description.affiliation Univ São Paulo, Fac Med, Inst Psiquiatria, Lab Neurociencias LIM 27, São Paulo, Brazil
dc.description.affiliationUnifesp Hosp Rim & Hipertensao UNIFESP, São Paulo, Brazil
dc.description.sponsorshipID Financiadora de Estudos e Projetos (Finep): 01.08.01230.00
dc.identifier.doi 10.2217/PGS.11.70
dc.description.source Web of Science
dc.identifier.wos WOS:000295728800016



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