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The impact of CYP3A4 and CYP3A5 genetic variations on tacrolimus treatment of living‐donor Egyptian kidney transplanted patients
BACKGROUND: Tacrolimus (TAC) is the mainstay of immunosuppressive regimen for kidney transplantations. Its clinical use is complex due to high inter‐individual variations which can be partially attributed to genetic variations at the metabolizing enzymes CYP3A4 and CYP3A5. Two single nucleotide poly...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681408/ https://www.ncbi.nlm.nih.gov/pubmed/37789683 http://dx.doi.org/10.1002/jcla.24969 |
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author | Wanas, Hanaa Kamel, Mai Hamed William, Emad Adel Fayad, Tarek Abdelfattah, Mohamed Essmat Elbadawy, Hossein Mostafa Mikhael, Emily Samir |
author_facet | Wanas, Hanaa Kamel, Mai Hamed William, Emad Adel Fayad, Tarek Abdelfattah, Mohamed Essmat Elbadawy, Hossein Mostafa Mikhael, Emily Samir |
author_sort | Wanas, Hanaa |
collection | PubMed |
description | BACKGROUND: Tacrolimus (TAC) is the mainstay of immunosuppressive regimen for kidney transplantations. Its clinical use is complex due to high inter‐individual variations which can be partially attributed to genetic variations at the metabolizing enzymes CYP3A4 and CYP3A5. Two single nucleotide polymorphisms (SNPs), CYP3A4*22 and CYP3A5*3, have been reported as important causes of differences in pharmacokinetics that can affect efficacy and/or toxicity of TAC. OBJECTIVE: Investigating the effect of CYP3A4*22 and CYP3A5*3 SNPs individually and in combination on the TAC concentration in Egyptian renal recipients. METHODS: Overall, 72 Egyptian kidney transplant recipients were genotyped for CYP3A4*22 G>A and CYP3A5*3 T>C. According to the functional defect associated with CYP3A variants, patients were clustered into: poor (PM) and non‐poor metabolizers (Non‐PM). The impact on dose adjusted through TAC concentrations (C0) and daily doses at different time points after transplantation was evaluated. RESULTS: Cyp3A4*1/*22 and PM groups require significantly lower dose of TAC (mg/kg) at different time points with significantly higher concentration/dose (C0/D) ratio at day 10 in comparison to Cyp3A4*1/*1 and Non‐PM groups respectively. However, CyP3A5*3 heterozygous individuals did not show any significant difference in comparison to CyP3A5*1/*3 individuals. By comparing between PM and Non‐PM, the PM group had a significantly lower rate of recipients not reaching target C0 at day 14. CONCLUSION: This is the first study on Egyptian population to investigate the impact of CYP3A4*22 and CYP3A5*3 SNPs individually and in combination on the TAC concentration. This study and future multicenter studies can contribute to the individualization of TAC dosing in Egyptian patients. |
format | Online Article Text |
id | pubmed-10681408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106814082023-10-03 The impact of CYP3A4 and CYP3A5 genetic variations on tacrolimus treatment of living‐donor Egyptian kidney transplanted patients Wanas, Hanaa Kamel, Mai Hamed William, Emad Adel Fayad, Tarek Abdelfattah, Mohamed Essmat Elbadawy, Hossein Mostafa Mikhael, Emily Samir J Clin Lab Anal Research Articles BACKGROUND: Tacrolimus (TAC) is the mainstay of immunosuppressive regimen for kidney transplantations. Its clinical use is complex due to high inter‐individual variations which can be partially attributed to genetic variations at the metabolizing enzymes CYP3A4 and CYP3A5. Two single nucleotide polymorphisms (SNPs), CYP3A4*22 and CYP3A5*3, have been reported as important causes of differences in pharmacokinetics that can affect efficacy and/or toxicity of TAC. OBJECTIVE: Investigating the effect of CYP3A4*22 and CYP3A5*3 SNPs individually and in combination on the TAC concentration in Egyptian renal recipients. METHODS: Overall, 72 Egyptian kidney transplant recipients were genotyped for CYP3A4*22 G>A and CYP3A5*3 T>C. According to the functional defect associated with CYP3A variants, patients were clustered into: poor (PM) and non‐poor metabolizers (Non‐PM). The impact on dose adjusted through TAC concentrations (C0) and daily doses at different time points after transplantation was evaluated. RESULTS: Cyp3A4*1/*22 and PM groups require significantly lower dose of TAC (mg/kg) at different time points with significantly higher concentration/dose (C0/D) ratio at day 10 in comparison to Cyp3A4*1/*1 and Non‐PM groups respectively. However, CyP3A5*3 heterozygous individuals did not show any significant difference in comparison to CyP3A5*1/*3 individuals. By comparing between PM and Non‐PM, the PM group had a significantly lower rate of recipients not reaching target C0 at day 14. CONCLUSION: This is the first study on Egyptian population to investigate the impact of CYP3A4*22 and CYP3A5*3 SNPs individually and in combination on the TAC concentration. This study and future multicenter studies can contribute to the individualization of TAC dosing in Egyptian patients. John Wiley and Sons Inc. 2023-10-03 /pmc/articles/PMC10681408/ /pubmed/37789683 http://dx.doi.org/10.1002/jcla.24969 Text en © 2023 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Wanas, Hanaa Kamel, Mai Hamed William, Emad Adel Fayad, Tarek Abdelfattah, Mohamed Essmat Elbadawy, Hossein Mostafa Mikhael, Emily Samir The impact of CYP3A4 and CYP3A5 genetic variations on tacrolimus treatment of living‐donor Egyptian kidney transplanted patients |
title | The impact of CYP3A4 and CYP3A5 genetic variations on tacrolimus treatment of living‐donor Egyptian kidney transplanted patients |
title_full | The impact of CYP3A4 and CYP3A5 genetic variations on tacrolimus treatment of living‐donor Egyptian kidney transplanted patients |
title_fullStr | The impact of CYP3A4 and CYP3A5 genetic variations on tacrolimus treatment of living‐donor Egyptian kidney transplanted patients |
title_full_unstemmed | The impact of CYP3A4 and CYP3A5 genetic variations on tacrolimus treatment of living‐donor Egyptian kidney transplanted patients |
title_short | The impact of CYP3A4 and CYP3A5 genetic variations on tacrolimus treatment of living‐donor Egyptian kidney transplanted patients |
title_sort | impact of cyp3a4 and cyp3a5 genetic variations on tacrolimus treatment of living‐donor egyptian kidney transplanted patients |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681408/ https://www.ncbi.nlm.nih.gov/pubmed/37789683 http://dx.doi.org/10.1002/jcla.24969 |
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