Influence of CYP3A4 and CYP3A5 polymorphisms on tacrolimus and sirolimus exposure in stable kidney transplant recipients
-
Erika Y. Tamashiro
,
Claudia R. Felipe
Abstract
Background:
Polymorphisms in genes encoding for drug-metabolizing enzymes and drug transporters are among multiple factors that modulate the pharmacokinetic variability of tacrolimus (TAC) and sirolimus (SRL). This study aimed to evaluate the influence of single nucleotide polymorphisms (SNPs) on TAC and SRL dose-adjusted concentrations (C0/D) in stable kidney transplant recipients.
Methods:
This is an exploratory and prospective study, which includes 46 stable kidney transplant recipients. These patients were monitored from the 3rd to the 24th month after transplantation. The SRL group consisted of 25 patients receiving TAC, prednisone (PRED), and mycophenolate sodium (MPS), which were converted from TAC to SRL at 3rd month after transplantation. The TAC group consisted of 21 patients who underwent treatment with TAC, PRED, and MPS. Both groups were genotyped for CYP3A4 rs2242480 (g.20230G>A), CYP3A5 rs15524 (g.31611C>T), CYP2C8 rs10509681 (c.1196A>G) and ABCB1 rs1045642 (c.3435C>T), rs1128503 (c.1236C>T), and rs2032582 (c.2677G>T/A) polymorphisms.
Results:
In the TAC group, CYP3A4 rs2242480 A allele carriers were associated with lower TAC C0/D. For CYP3A5 rs15524 SNP, C0/D was higher among patients carrying TT genotype when compared with CT and CC genotype carriers in the SRL and, more consistently, in the TAC groups. For ABCB1 rs1045642 SNP, TT genotype was associated with reduced SRL C0/D, but only at month 15.
Conclusions:
CYP3A4 rs2242480 and CYP3A5 rs15524 SNPs resulted in significant changes in SRL and TAC C0/D at different times after transplantation.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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Supplemental Material:
The online version of this article (DOI: https://doi.org/10.1515/dmpt-2016-0036) offers supplementary material, available to authorized users.
©2017 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review
- An update on HLA alleles associated with adverse drug reactions
- Original Articles
- Influence of CYP3A4 and CYP3A5 polymorphisms on tacrolimus and sirolimus exposure in stable kidney transplant recipients
- Novel therapeutic approaches of natural oil from black seeds and its underlying mechanisms against kidney dysfunctions in haloperidol-induced male rats
- Evaluation of genotype-guided acenocoumarol dosing algorithms in Russian patients
- Letter to the Editor
- Pharmacogenetics-based optimisation of atazanavir treatment: potential role of new genetic predictors
- Congress Report
- 8th Santorini Conference: Systems medicine and personalized health and therapy, Santorini, Greece, 3–5 October 2016
Artikel in diesem Heft
- Frontmatter
- Review
- An update on HLA alleles associated with adverse drug reactions
- Original Articles
- Influence of CYP3A4 and CYP3A5 polymorphisms on tacrolimus and sirolimus exposure in stable kidney transplant recipients
- Novel therapeutic approaches of natural oil from black seeds and its underlying mechanisms against kidney dysfunctions in haloperidol-induced male rats
- Evaluation of genotype-guided acenocoumarol dosing algorithms in Russian patients
- Letter to the Editor
- Pharmacogenetics-based optimisation of atazanavir treatment: potential role of new genetic predictors
- Congress Report
- 8th Santorini Conference: Systems medicine and personalized health and therapy, Santorini, Greece, 3–5 October 2016
