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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Pharmacogenetics and Pharmacogenomics

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1538432

This article is part of the Research Topic Editor's Feature: Negative Findings in Pharmacogenetics and Pharmacogenomics Volume II View all 6 articles

Impact of CYP3A4 and ABCB1 genetic variants on Tacrolimus dosing in Greek Kidney Transplant Recipients

Provisionally accepted
George P Patrinos George P Patrinos 1*Anna Tsironi Anna Tsironi 2Konstantinos Lazaros Konstantinos Lazaros 3Effrosyni Mendrinou Effrosyni Mendrinou 2Marios Papasotiriou Marios Papasotiriou 2Stavroula Siamoglou Stavroula Siamoglou 2Kyriaki Kydonopoulou Kyriaki Kydonopoulou 4Anne John Anne John 5Alexandra Gerou Alexandra Gerou 4Spyridon Gerou Spyridon Gerou 4Bassam R Ali Bassam R Ali 5Aristidis G Vrahatis Aristidis G Vrahatis 3
  • 1 Department of Pharmacy, University of Patras, Patras, Greece
  • 2 University of Patras, Patras, Western Greece, Greece
  • 3 Ionian University, Corfu, Greece
  • 4 ANALYSI, Thessaloniki, Greece
  • 5 United Arab Emirates University, Al-Ain, Abu Dhabi, United Arab Emirates

The final, formatted version of the article will be published soon.

    Background: Tacrolimus, an approved first-line calcineurin inhibitor, is widely prescribed in organ transplantation to prevent allograft rejection. Its narrow therapeutic index requires precise management to achieve optimal dosing and to minimize adverse drug events (ADEs) while ensuring its therapeutic efficacy. Among several factors, genetic differences contribute significantly to the inter-individual and inter-ethnic variability in pharmacokinetics (PK) of tacrolimus in kidney transplant recipients. As a result, investigating the role of genetic variation in Greek transplant recipients becomes crucial to optimizing therapeutic strategies and enhancing the efficacy of immunosuppressive treatment.: Genetic variants which are known to influence the activity of enzymes or drug-transporters critical to tacrolimus pharmacokinetics, may significantly affect the required kidney post-transplant tacrolimus daily dose. Aim: To assess the correlation of ABCB1 genetic variants (rs1128503, rs2229109) and CYP3A4 (rs2242480, rs4986910) with tacrolimus dose-adjusted trough concentration (C0/D), in Greek kidney transplant recipients. Methods: Ninety-four unrelated Greek kidney transplant recipients were included in this study from the Nephrology Clinic of the University General Hospital of Patras. Patients' dose-adjusted trough levels were measured at five distinct time points after transplantation and analyzed in relation to the possible influence of CYP3A4 and correlated with the abovementioned ABCB1 genetic variants using standard genotyping analysis and Sanger sequencing.The genetic variants rs1128503, rs2229109, rs2242480, rs4986910 did not show any significant association with the daily dosing requirements of tacrolimus for at least one year, in Greek patients who have undergone kidney transplantation.It remains uncertain whether these genetic variants influence the assessment of the appropriate tacrolimus dosing one year after transplantation in Greek kidney transplant recipients.

    Keywords: Kidney Transplantation, Tacrolimus, FK506, C/D ratio, Greek population

    Received: 02 Dec 2024; Accepted: 27 Feb 2025.

    Copyright: © 2025 Patrinos, Tsironi, Lazaros, Mendrinou, Papasotiriou, Siamoglou, Kydonopoulou, John, Gerou, Gerou, Ali and Vrahatis. 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) or licensor 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.

    * Correspondence: George P Patrinos, Department of Pharmacy, University of Patras, Patras, GR-26504, Greece

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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