Pharmacogenetics of calcineurin inhibitors in Brazilian renal transplant patients

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art_SANTORO_Pharmacogenetics_of_calcineurin_inhibitors_in_Brazilian_renal_transplant_2011.PDF (706.89 KB)
Citações na Scopus
42
Tipo de produção
article
Data de publicação
2011
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
FUTURE MEDICINE LTD
Autores
SANTORO, Ana
FELIPE, Claudia R.
TEDESCO-SILVA, Helio
MEDINA-PESTANA, Jose O.
STRUCHINER, Claudio J.
SUAREZ-KURTZ, Guilherme
Citação
PHARMACOGENOMICS, v.12, n.9, p.1293-1303, 2011
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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
Palavras-chave
ABCB1, Brazil, calcineurin inhibitors, cyclosporine, CYP3A5, renal transplant, tacrolimus
URI
https://observatorio.fm.usp.br/handle/OPI/23383
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MPS