Donor ABCB1 genetic polymorphisms influence epithelial-to-mesenchyme transition in tacrolimus-treated kidney recipients.
Pharmacogenomics
; 15(16): 2011-24, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-25521359
ABSTRACT
AIM:
The contribution of epithelial-mesenchymal transition (EMT) has been suggested in renal transplant recipients receiving calcineurin inhibitors and developing nephrotoxicity. MATERIALS &METHODS:
We assessed whether interindividual variability in tacrolimus pharmacokinetics is associated with the occurrence in tubular cells of two EMT markers (vimentin, ß-catenin) detected at 3-month in 140 allograft biopsies. We investigated whether genetic polymorphisms affecting CYP3A5 and ABCB1 influence EMT and kidney fibrosis.RESULTS:
In univariate analysis, the donor CYP3A5*1 allele was significantly associated with a lower vimentin expression. In multivariate analysis, grafts carrying ABCB1 3435T allele(s) developed significantly less EMT and less interstitial fibrosis.CONCLUSION:
Donor SNPs significantly influence the epithelial program in the context of kidney transplantation, and the epithelial metabolism of tacrolimus is one key to understand graft fibrogenesis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante de Rim
/
Tacrolimo
/
Citocromo P-450 CYP3A
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Nefropatias
Limite:
Adult
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article