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CYP3A5 Gene-Guided Tacrolimus Treatment of Living-Donor Egyptian Kidney Transplanted Patients

BACKGROUND: Tacrolimus is an approved first-line immunosuppressive agent for kidney transplantations. Part of interindividual and interethnic differences in the response of patients to tacrolimus is attributed to polymorphisms at CYP3A5 metabolic enzyme. CYP3A5 gene expression status is associated w...

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Autores principales: Mendrinou, Effrosyni, Mashaly, Mohamed Elsayed, Al Okily, Amir Mohamed, Mohamed, Mohamed Elsayed, Refaie, Ayman Fathi, Elsawy, Essam Mahmoud, Saleh, Hazem Hamed, Sheashaa, Hussein, Patrinos, George P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431691/
https://www.ncbi.nlm.nih.gov/pubmed/32848803
http://dx.doi.org/10.3389/fphar.2020.01218
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author Mendrinou, Effrosyni
Mashaly, Mohamed Elsayed
Al Okily, Amir Mohamed
Mohamed, Mohamed Elsayed
Refaie, Ayman Fathi
Elsawy, Essam Mahmoud
Saleh, Hazem Hamed
Sheashaa, Hussein
Patrinos, George P.
author_facet Mendrinou, Effrosyni
Mashaly, Mohamed Elsayed
Al Okily, Amir Mohamed
Mohamed, Mohamed Elsayed
Refaie, Ayman Fathi
Elsawy, Essam Mahmoud
Saleh, Hazem Hamed
Sheashaa, Hussein
Patrinos, George P.
author_sort Mendrinou, Effrosyni
collection PubMed
description BACKGROUND: Tacrolimus is an approved first-line immunosuppressive agent for kidney transplantations. Part of interindividual and interethnic differences in the response of patients to tacrolimus is attributed to polymorphisms at CYP3A5 metabolic enzyme. CYP3A5 gene expression status is associated with tacrolimus dose requirement in renal transplant recipients. MATERIALS AND METHODS: In this study, we determined the allelic frequency of CYP3A5*3 in 76 renal transplanted patients of Egyptian descent. Secondly, we evaluated the influence of the CYP3A5 gene variant on tacrolimus doses required for these patients as well on dose-adjusted tacrolimus trough-concentrations. RESULTS: The CYP3A5*3 variant was the most frequent allele detected at 85.53%. Additionally, our results showed that, mean tacrolimus daily requirements for heterozygous patients (CYP3A5*1/*3) were significantly higher compared to homozygous patients (CYP3A5*3/*3) during the first year after kidney transplantation. CONCLUSION: This is the first study in Egypt contributing to the individualization of tacrolimus dosing in Egyptian patients, informed by the CYP3A5 genotype.
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spelling pubmed-74316912020-08-25 CYP3A5 Gene-Guided Tacrolimus Treatment of Living-Donor Egyptian Kidney Transplanted Patients Mendrinou, Effrosyni Mashaly, Mohamed Elsayed Al Okily, Amir Mohamed Mohamed, Mohamed Elsayed Refaie, Ayman Fathi Elsawy, Essam Mahmoud Saleh, Hazem Hamed Sheashaa, Hussein Patrinos, George P. Front Pharmacol Pharmacology BACKGROUND: Tacrolimus is an approved first-line immunosuppressive agent for kidney transplantations. Part of interindividual and interethnic differences in the response of patients to tacrolimus is attributed to polymorphisms at CYP3A5 metabolic enzyme. CYP3A5 gene expression status is associated with tacrolimus dose requirement in renal transplant recipients. MATERIALS AND METHODS: In this study, we determined the allelic frequency of CYP3A5*3 in 76 renal transplanted patients of Egyptian descent. Secondly, we evaluated the influence of the CYP3A5 gene variant on tacrolimus doses required for these patients as well on dose-adjusted tacrolimus trough-concentrations. RESULTS: The CYP3A5*3 variant was the most frequent allele detected at 85.53%. Additionally, our results showed that, mean tacrolimus daily requirements for heterozygous patients (CYP3A5*1/*3) were significantly higher compared to homozygous patients (CYP3A5*3/*3) during the first year after kidney transplantation. CONCLUSION: This is the first study in Egypt contributing to the individualization of tacrolimus dosing in Egyptian patients, informed by the CYP3A5 genotype. Frontiers Media S.A. 2020-08-11 /pmc/articles/PMC7431691/ /pubmed/32848803 http://dx.doi.org/10.3389/fphar.2020.01218 Text en Copyright © 2020 Mendrinou, Mashaly, Al Okily, Mohamed, Refaie, Elsawy, Saleh, Sheashaa and Patrinos http://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
Mendrinou, Effrosyni
Mashaly, Mohamed Elsayed
Al Okily, Amir Mohamed
Mohamed, Mohamed Elsayed
Refaie, Ayman Fathi
Elsawy, Essam Mahmoud
Saleh, Hazem Hamed
Sheashaa, Hussein
Patrinos, George P.
CYP3A5 Gene-Guided Tacrolimus Treatment of Living-Donor Egyptian Kidney Transplanted Patients
title CYP3A5 Gene-Guided Tacrolimus Treatment of Living-Donor Egyptian Kidney Transplanted Patients
title_full CYP3A5 Gene-Guided Tacrolimus Treatment of Living-Donor Egyptian Kidney Transplanted Patients
title_fullStr CYP3A5 Gene-Guided Tacrolimus Treatment of Living-Donor Egyptian Kidney Transplanted Patients
title_full_unstemmed CYP3A5 Gene-Guided Tacrolimus Treatment of Living-Donor Egyptian Kidney Transplanted Patients
title_short CYP3A5 Gene-Guided Tacrolimus Treatment of Living-Donor Egyptian Kidney Transplanted Patients
title_sort cyp3a5 gene-guided tacrolimus treatment of living-donor egyptian kidney transplanted patients
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431691/
https://www.ncbi.nlm.nih.gov/pubmed/32848803
http://dx.doi.org/10.3389/fphar.2020.01218
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