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Pharmacogenomics
Article . 2015 . Peer-reviewed
Data sources: Crossref
Pharmacogenomics
Article . 2016
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Relationship Between mRNA Expression Levels of CYP3A4, CYP3A5 and SXR in Peripheral Mononuclear Blood Cells and Aging in Young Kidney Transplant Recipients Under Tacrolimus Treatment

Authors: M. Ferraresso; S. Turolo; M. Belingheri; A. S. Tirelli; I. Cortinovis; S. Milani; A. Edefonti; +1 Authors

Relationship Between mRNA Expression Levels of CYP3A4, CYP3A5 and SXR in Peripheral Mononuclear Blood Cells and Aging in Young Kidney Transplant Recipients Under Tacrolimus Treatment

Abstract

The activity of several key enzymes involved in the metabolism of many drugs is subject to change closely related to the age of patients. This possibility must also be considered in the case of tacrolimus, the most important calcineurins inhibitor, which is widely used in pediatric kidney transplantation. As well as in the liver and intestine, some of the enzymes involved in the metabolism of tacrolimus were also isolated in the peripheral blood mononuclear cells (PBMCs), where also appear to play an important regulatory action. Therefore, the influence of some external factors on the expression of specific mRNA can be determined noninvasively.The correlation between the levels of mRNA specific for key enzymes SXR, CYP3A and ABCB1 involved in the metabolism of tacrolimus was evaluated in PBMCs obtained from a selected population of 29 young kidney transplant recipients. A possible correlation between the expression of these specific mRNAs and tacrolimus pharmacokinetics was also investigated.The patients' age and their blood concentrations of SXR mRNA were directly correlated with the expression of CYP3A4, CYP3A5 mRNAs, but not of ABCB1 mRNA in the PBMCs. tacrolimus-normalized daily dose was strongly correlated with patient's age and multivariable regression indicates the CYP3A4-specific mRNA as the sole independent variable influencing tacrolimus concentration-to-dose ratio.Aging and SXR mRNA significantly affect the expression of CYP3A4- and CYP3A5-specific mRNA as measured by their concentration in PBMC.

Country
Italy
Keywords

Male, Aging, Receptors, Steroid, ATP Binding Cassette Transporter, Subfamily B, Adolescent, Pregnane X Receptor, Kidney Transplantation, Monocytes, Tacrolimus, ABCB1; CYP3A4; CYP3A5; mRNA; Pediatric kidney transplant; Peripheral blood mononuclear cells; SXR; Tacrolimus; Pharmacology; Genetics; Molecular Medicine, Cytochrome P-450 CYP3A, Humans, Female, RNA, Messenger, Immunosuppressive Agents

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
4
Average
Average
Average
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