Journal Article

<i>CYP3A5</i> and <i>ABCB1</i> polymorphisms in donor and recipient: impact on Tacrolimus dose requirements and clinical outcome after renal transplantation

François Glowacki, Arnaud Lionet, David Buob, Myriam Labalette, Delphine Allorge, François Provôt, Marc Hazzan, Christian Noël, Franck Broly and Christelle Cauffiez

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 26, issue 9, pages 3046-3050
Published in print September 2011 | ISSN: 0931-0509
Published online June 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr253
CYP3A5 and ABCB1 polymorphisms in donor and recipient: impact on Tacrolimus dose requirements and clinical outcome after renal transplantation

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Background. The effect of potentially relevant genetic polymorphisms, CYP3A5 6986A>G and ABCB1 3435C>T, on Tacrolimus pharmacokinetics and graft clinical outcome was investigated in donor and recipient DNA samples from 209 kidney transplant patients.

Methodology/principal findings. The mean follow-up was 21.8 ± 9 months. The Tacrolimus dose, trough blood concentrations (C0) and C0/dose ratio were only statistically correlated with the recipient CYP3A5 genotype. CYP3A5 and ABCB1 genotypes appeared to have no influence on the incidence of Biopsy Proven Acute Rejection and Delayed Graft Function. Renal function was not affected by CYP3A5 and ABCB1 genotypes. Histological evaluation of biopsies revealed also no significant association between Tacrolimus toxicity features and donor or recipient CYP3A5 and ABCB1 polymorphisms. Tacrolimus sparing appeared to be independent of CYP3A5 and ABCB1 genotypes.

Conclusions/significance. Recipient CYP3A5 6986A>G polymorphism explains part of the interindividual variability of the pharmacokinetics of Tacrolimus. The clinical outcome at 2-year follow-up does not appear to be related to the donor or recipient CYP3A5 6986A>G and/or ABCB1 3435C>T polymorphisms.

Keywords: pharmacogenetics; tacrolimus; transplantation

Journal Article.  1814 words.  Illustrated.

Subjects: Nephrology

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