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Effect of CYP3A4, CYP3A5, MDR1 and POR Genetic Polymorphisms in Immunosuppressive Treatment in Chilean Kidney Transplanted Patients
Cyclosporine (CsA) and tacrolimus (TAC) are immunosuppressant drugs characterized by a narrow therapeutic range and high pharmacokinetic variability. The effect of polymorphisms in genes related to the metabolism and transport of these drugs, namely CYP3A4, CYP3A5, MDR1 and POR genes, has been evalu...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685429/ https://www.ncbi.nlm.nih.gov/pubmed/34938174 http://dx.doi.org/10.3389/fphar.2021.674117 |
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author | Contreras-Castillo, Stephania Plaza, Anita Stojanova, Jana Navarro, Gustavo Carmona, Rodolfo Corvalán, Fernando Cerpa, Leslie Sandoval, Christopher Muñoz, Daniel Leiva, Marina Castañeda, Luis E. Farias, Nayaret Alvarez, Carolina Llull, Gabriel Mezzano, Sergio Ardiles, Leopoldo Varela, Nelson Rodríguez, María S. Flores, Claudio Cayún, Juan Pablo Krall, Paola Quiñones, Luis A. |
author_facet | Contreras-Castillo, Stephania Plaza, Anita Stojanova, Jana Navarro, Gustavo Carmona, Rodolfo Corvalán, Fernando Cerpa, Leslie Sandoval, Christopher Muñoz, Daniel Leiva, Marina Castañeda, Luis E. Farias, Nayaret Alvarez, Carolina Llull, Gabriel Mezzano, Sergio Ardiles, Leopoldo Varela, Nelson Rodríguez, María S. Flores, Claudio Cayún, Juan Pablo Krall, Paola Quiñones, Luis A. |
author_sort | Contreras-Castillo, Stephania |
collection | PubMed |
description | Cyclosporine (CsA) and tacrolimus (TAC) are immunosuppressant drugs characterized by a narrow therapeutic range and high pharmacokinetic variability. The effect of polymorphisms in genes related to the metabolism and transport of these drugs, namely CYP3A4, CYP3A5, MDR1 and POR genes, has been evaluated in diverse populations. However, the impact of these polymorphisms on drug disposition is not well established in Latin American populations. Using TaqMan® probes, we determined the allelic frequency of seven variants in CYP3A4, CYP3A5, MDR1 and POR in 139 Chilean renal transplant recipients, of which 89 were treated with CsA and 50 with TAC. We tested associations between variants and trough and/or 2-hour concentrations, normalized by dose (C(0)/D and C(2)/D) at specific time points post-transplant. We found that CYP3A5*3/*3 carriers required lower doses of TAC. In TAC treated patients, most CYP3A5*3/*3 carriers presented higher C(0)/D and a high proportion of patients with C(0) levels outside the therapeutic range relative to other genotypes. These results reinforce the value of considering CYP3A5 genotypes alongside therapeutic drug monitoring for TAC treated Chilean kidney recipients. |
format | Online Article Text |
id | pubmed-8685429 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86854292021-12-21 Effect of CYP3A4, CYP3A5, MDR1 and POR Genetic Polymorphisms in Immunosuppressive Treatment in Chilean Kidney Transplanted Patients Contreras-Castillo, Stephania Plaza, Anita Stojanova, Jana Navarro, Gustavo Carmona, Rodolfo Corvalán, Fernando Cerpa, Leslie Sandoval, Christopher Muñoz, Daniel Leiva, Marina Castañeda, Luis E. Farias, Nayaret Alvarez, Carolina Llull, Gabriel Mezzano, Sergio Ardiles, Leopoldo Varela, Nelson Rodríguez, María S. Flores, Claudio Cayún, Juan Pablo Krall, Paola Quiñones, Luis A. Front Pharmacol Pharmacology Cyclosporine (CsA) and tacrolimus (TAC) are immunosuppressant drugs characterized by a narrow therapeutic range and high pharmacokinetic variability. The effect of polymorphisms in genes related to the metabolism and transport of these drugs, namely CYP3A4, CYP3A5, MDR1 and POR genes, has been evaluated in diverse populations. However, the impact of these polymorphisms on drug disposition is not well established in Latin American populations. Using TaqMan® probes, we determined the allelic frequency of seven variants in CYP3A4, CYP3A5, MDR1 and POR in 139 Chilean renal transplant recipients, of which 89 were treated with CsA and 50 with TAC. We tested associations between variants and trough and/or 2-hour concentrations, normalized by dose (C(0)/D and C(2)/D) at specific time points post-transplant. We found that CYP3A5*3/*3 carriers required lower doses of TAC. In TAC treated patients, most CYP3A5*3/*3 carriers presented higher C(0)/D and a high proportion of patients with C(0) levels outside the therapeutic range relative to other genotypes. These results reinforce the value of considering CYP3A5 genotypes alongside therapeutic drug monitoring for TAC treated Chilean kidney recipients. Frontiers Media S.A. 2021-12-06 /pmc/articles/PMC8685429/ /pubmed/34938174 http://dx.doi.org/10.3389/fphar.2021.674117 Text en Copyright © 2021 Contreras-Castillo, Plaza, Stojanova, Navarro, Carmona, Corvalán, Cerpa, Sandoval, Muñoz, Leiva, Castañeda, Farias, Alvarez, Llull, Mezzano, Ardiles, Varela, Rodríguez, Flores, Cayún, Krall and Quiñones. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Contreras-Castillo, Stephania Plaza, Anita Stojanova, Jana Navarro, Gustavo Carmona, Rodolfo Corvalán, Fernando Cerpa, Leslie Sandoval, Christopher Muñoz, Daniel Leiva, Marina Castañeda, Luis E. Farias, Nayaret Alvarez, Carolina Llull, Gabriel Mezzano, Sergio Ardiles, Leopoldo Varela, Nelson Rodríguez, María S. Flores, Claudio Cayún, Juan Pablo Krall, Paola Quiñones, Luis A. Effect of CYP3A4, CYP3A5, MDR1 and POR Genetic Polymorphisms in Immunosuppressive Treatment in Chilean Kidney Transplanted Patients |
title | Effect of CYP3A4, CYP3A5, MDR1 and POR Genetic Polymorphisms in Immunosuppressive Treatment in Chilean Kidney Transplanted Patients |
title_full | Effect of CYP3A4, CYP3A5, MDR1 and POR Genetic Polymorphisms in Immunosuppressive Treatment in Chilean Kidney Transplanted Patients |
title_fullStr | Effect of CYP3A4, CYP3A5, MDR1 and POR Genetic Polymorphisms in Immunosuppressive Treatment in Chilean Kidney Transplanted Patients |
title_full_unstemmed | Effect of CYP3A4, CYP3A5, MDR1 and POR Genetic Polymorphisms in Immunosuppressive Treatment in Chilean Kidney Transplanted Patients |
title_short | Effect of CYP3A4, CYP3A5, MDR1 and POR Genetic Polymorphisms in Immunosuppressive Treatment in Chilean Kidney Transplanted Patients |
title_sort | effect of cyp3a4, cyp3a5, mdr1 and por genetic polymorphisms in immunosuppressive treatment in chilean kidney transplanted patients |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685429/ https://www.ncbi.nlm.nih.gov/pubmed/34938174 http://dx.doi.org/10.3389/fphar.2021.674117 |
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