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Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants
Cytochrome P450 (CYP) enzymes, such as CYP3A4, and CYP3A5, P450 oxidoreductase (POR), peroxisome proliferator activated receptor alpha (PPAR-alpha), and drug transporter (ABCB1) were observed to influence concentrations of immunosuppressants (cyclosporine, everolimus, sirolimus, and tacrolimus) and...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147030/ https://www.ncbi.nlm.nih.gov/pubmed/35629245 http://dx.doi.org/10.3390/jpm12050823 |
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author | Sridharan, Kannan Shah, Shamik Jassim, Anfal Hammad, Mona Ebrahim Al Gadhban, Johaina Al Segai, Ola |
author_facet | Sridharan, Kannan Shah, Shamik Jassim, Anfal Hammad, Mona Ebrahim Al Gadhban, Johaina Al Segai, Ola |
author_sort | Sridharan, Kannan |
collection | PubMed |
description | Cytochrome P450 (CYP) enzymes, such as CYP3A4, and CYP3A5, P450 oxidoreductase (POR), peroxisome proliferator activated receptor alpha (PPAR-alpha), and drug transporter (ABCB1) were observed to influence concentrations of immunosuppressants (cyclosporine, everolimus, sirolimus, and tacrolimus) and outcomes in renal transplants. We carried out the present study to evaluate the prevalence and impact of these single nucleotide polymorphisms (SNPs) in adult renal transplants. SNPs were evaluated using commercial TaqMan(®) assays. Serum drug concentrations were estimated using immunoassays. One hundred and forty-six patients were recruited. SNPs in CYP3A5*3 were significantly associated with greater dose-adjusted cyclosporine and tacrolimus concentrations. SNPs in POR*28 were observed with significantly lower dose-adjusted concentrations, particularly with cyclosporine and tacrolimus. ABCB1 homozygous polymorphisms were observed with significantly lower time spent in the therapeutic range with cyclosporine and everolimus/sirolimus. Cyclosporine was observed in a significantly greater proportion of patients with elevated GGT, and SNPs in PPAR-alpha were significantly associated with an increased risk of this adverse event. Hypertriglyceridemia with everolimus was significantly associated with POR*28 polymorphisms. There is a need to validate the influence of these SNPs in a prospective study and develop an algorithm predicting the achievement of target concentrations. |
format | Online Article Text |
id | pubmed-9147030 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91470302022-05-29 Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants Sridharan, Kannan Shah, Shamik Jassim, Anfal Hammad, Mona Ebrahim Al Gadhban, Johaina Al Segai, Ola J Pers Med Article Cytochrome P450 (CYP) enzymes, such as CYP3A4, and CYP3A5, P450 oxidoreductase (POR), peroxisome proliferator activated receptor alpha (PPAR-alpha), and drug transporter (ABCB1) were observed to influence concentrations of immunosuppressants (cyclosporine, everolimus, sirolimus, and tacrolimus) and outcomes in renal transplants. We carried out the present study to evaluate the prevalence and impact of these single nucleotide polymorphisms (SNPs) in adult renal transplants. SNPs were evaluated using commercial TaqMan(®) assays. Serum drug concentrations were estimated using immunoassays. One hundred and forty-six patients were recruited. SNPs in CYP3A5*3 were significantly associated with greater dose-adjusted cyclosporine and tacrolimus concentrations. SNPs in POR*28 were observed with significantly lower dose-adjusted concentrations, particularly with cyclosporine and tacrolimus. ABCB1 homozygous polymorphisms were observed with significantly lower time spent in the therapeutic range with cyclosporine and everolimus/sirolimus. Cyclosporine was observed in a significantly greater proportion of patients with elevated GGT, and SNPs in PPAR-alpha were significantly associated with an increased risk of this adverse event. Hypertriglyceridemia with everolimus was significantly associated with POR*28 polymorphisms. There is a need to validate the influence of these SNPs in a prospective study and develop an algorithm predicting the achievement of target concentrations. MDPI 2022-05-19 /pmc/articles/PMC9147030/ /pubmed/35629245 http://dx.doi.org/10.3390/jpm12050823 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sridharan, Kannan Shah, Shamik Jassim, Anfal Hammad, Mona Ebrahim Al Gadhban, Johaina Al Segai, Ola Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants |
title | Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants |
title_full | Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants |
title_fullStr | Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants |
title_full_unstemmed | Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants |
title_short | Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants |
title_sort | evaluation of pharmacogenetics of drug-metabolizing enzymes and drug efflux transporter in renal transplants receiving immunosuppressants |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147030/ https://www.ncbi.nlm.nih.gov/pubmed/35629245 http://dx.doi.org/10.3390/jpm12050823 |
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