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.
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.
Authors: Julia M Barbarino; Christine E Staatz; Raman Venkataramanan; Teri E Klein; Russ B Altman Journal: Pharmacogenet Genomics Date: 2013-10 Impact factor: 2.089
Authors: Megan V Yanik; Michael E Seifert; Jayme E Locke; Vera Hauptfeld-Dolejsek; Michael R Crowley; Gary R Cutter; Roslyn B Mannon; Daniel I Feig; Nita A Limdi Journal: Pediatr Transplant Date: 2019-05-24
Authors: Nikola Z Stefanović; Tatjana P Cvetković; Tatjana M Jevtović-Stoimenov; Aleksandra M Ignjatović; Goran J Paunović; Radmila M Veličković Journal: Exp Ther Med Date: 2015-06-26 Impact factor: 2.447
Authors: S Zheng; Y Tasnif; M F Hebert; C L Davis; Y Shitara; J C Calamia; Y S Lin; D D Shen; K E Thummel Journal: Clin Pharmacol Ther Date: 2012-10-17 Impact factor: 6.875