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CYP3A5 and POR gene polymorphisms as predictors of infection and graft rejection in post-liver transplant patients treated with tacrolimus - a cohort study

The Pharmacogenomics Journal volume 25, Article number: 4 (2025) Cite this article

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Abstract

Liver transplantation is the only curative option for patients with advanced stages of liver disease, with tacrolimus used as the immunosuppressive drug of choice. Genetic variability can interfere with drug response, potentially leading to overexposure or underexposure. This study aims to investigate the association of CYP3A4 (rs2740574, rs2242480, rs35599367), CYP3A5 (rs776746, rs10264272), POR (rs1057868) and ABCB1 (rs1128503, rs2229109, rs9282564) gene polymorphisms with infection, acute rejection, and renal failure. The logistic regression model found an influence of CYP3A5 (rs776746) and POR28 (rs1057868) on the development of acute rejection after liver transplantation (p = 0.028). It also found an association between carriers of the variant allele of the POR*28 gene and infection.

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Fig. 1
Fig. 2: Association of POR gene (rs1057868) genotypes with infection.

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Data availability

Internal data management: After signing the informed consent form, clinical data was collected from the institution’s electronic medical records and databases and entered into the RedCAP platform (https://redcap.hc.fm.usp.br/). The polymorphism results were stored on the platform and on an institutional cloud drive (FMUSP). Only the researcher in charge and the master’s student have access to this data, which is protected by login and passwords. The data for statistical analysis with the other researchers was de-identified, thus ensuring the privacy, confidentiality and security of the participants.

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Acknowledgements

We would like to thank FAPESP, CNPQ and CAPES for funding the project. We would also like to thank everyone involved in carrying out the project: nursing staff, medical staff, postgraduate secretary, laboratory team. Their participation was essential to the project’s progress. We would like to thank the Department of Gastroenterology, which provided the data of the patients on the waiting list for liver transplantation, collected and stored the blood of the liver transplant patients and helped collect the information of the liver donors. The HC-FMUSP Pharmacy Division also helped with access to data on immunosuppressant prescriptions for transplant patients.

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Authors and Affiliations

  1. Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil

    Graziella D’ Agostino Ribeiro Naldi, Ariane Boccoli Minari, Lucas Nacif, Luiz Augusto Carneiro D Albuquerque, Eduardo Luiz Rachid Cançado & Suzane Kioko Ono

  2. Institute of Mathematics and Statistics of the University of São Paulo, São Paulo, Brazil

    Thales D. M. Pereira, Victor Fossaluza & Nicholas Wagner Eugenio

  3. Cell Biology Laboratory, University of São Paulo School of Medicine, São Paulo, Brazil

    Marcelo Alves Ferreira

  4. Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

    Guilherme H. Gregório

  5. Founder & co-CEO at Genera, São Paulo, Brazil

    Ricardo di Lazzaro Filho

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  1. Graziella D’ Agostino Ribeiro Naldi
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Contributions

GDARN: data curation, formal analysis, writing – original draft, investigation, methodology, review & editing; ABM: supervision, visualization, writing – review & editing; TDMP: data curation, formal analysis, writing – review & editing; VF: data curation, formal analysis, review & editing; MAF: data curation, formal analysis, review & editing; GHG: data curation, review & editing; LN: data curation, clinical analysis, investigation, methodology, review & editing; LACDA: review and editing, supervision; RL: data curation, review & editing; EL: data curation, review & editing; ELRC: review and editing, supervision, resources; SKO: conceptualization, data curation, funding acquisition, methodology, project administration, supervision, validation, visualization, writing – review & editing.

Corresponding author

Correspondence to Graziella D’ Agostino Ribeiro Naldi.

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Financial support statement

FAPESP: 2019/00945-1; CNPq: 308609/2018-2; GDARN: CAPES Scholarship. The opinions, hypotheses, conclusions, or recommendations expressed in this material are the sole responsibility of the authors and do not necessarily reflect FAPESP’s, CNPq’s or CAPES’s view.

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Naldi, G.D.A.R., Minari, A.B., Pereira, T.D.M. et al. CYP3A5 and POR gene polymorphisms as predictors of infection and graft rejection in post-liver transplant patients treated with tacrolimus - a cohort study. Pharmacogenomics J 25, 4 (2025). https://doi.org/10.1038/s41397-025-00363-4

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