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The pharmacogenetics of tacrolimus in renal transplant patients: association with tremors, new-onset diabetes and other clinical events

The Pharmacogenomics Journal volume 24, Article number: 3 (2024) Cite this article

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Abstract

Our study is the first study to investigate the effect of SNPs in CYP3A5, CYP3A4, ABCB1 and POR genes on the incidence of tremors, nephrotoxicity, and diabetes mellitus. A total of 223 renal transplant patients receiving tacrolimus and mycophenolate mofetil (MMF) were recruited. Both adults and children patients participated in the study. Genotyping was performed using PROFLEX-PCR followed by RFLP. MPA and tacrolimus plasma concentrations were measured by immunoassay. The AUC0-12h of MMF was estimated by a Bayesian method. We found a statistically significant association between the CYP3A5*3 and CYP3A4*1B genotypes and the tacrolimus exposure. We found a lower occurrence of nephrotoxicity (p = 0.03), tremor (p = 0.01), and new-onset diabetes (p = 0.002) associated with CYP3A5*1 allele. The CYP3A4*1B allele was significantly associated with a lower occurrence of new-onset diabetes (p = 0.026). The CYP3A5*1 allele was significantly associated with an increased risk of acute and chronic rejection (p = 0.03 and p < 0.001, respectively). Our results support the usefulness of tacrolimus pharmacokinetics in pre-kidney transplant assessments.

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The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This study was partially funded by the Tunisian Ministry of Higher Education, Scientific Research and Technology and the Ministry of Health

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Authors and Affiliations

  1. Biochemistry Department, LR12SP11, Sahloul University Hospital, Street Route Ceinture Sahloul, 4054, Sousse, Tunisia

    Amani Abderahmene, Yassine khalij, Amira Moussa, Meriam Ammar, Amel Ellouz, Dorra Amor, Houwaida Abbes, Mohamed Rayen Ganouni, Asma omezzine & Ali Bouslama

  2. University of Monastir, Faculty of Pharmacy of Monastir, Street Ibn Sina, 5000, Monastir, Tunisia

    Amani Abderahmene, Yassine khalij, Amira Moussa, Meriam Ammar, Amel Ellouz, Dorra Amor, Houwaida Abbes, Mohamed Rayen Ganouni, Asma omezzine & Ali Bouslama

  3. Nephrology Department, Sahloul University Hospital, Street Route Ceinture Sahloul, 4054, Sousse, Tunisia

    Wissal Sahtout & Dorsaf zellama

  4. Hematology Department, Fattouma Bourguiba University Hospital, 5000, Monastir, Tunisia

    Saoussen Chouchene

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  1. Amani Abderahmene
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Contributions

This study was supervised by AO and AB. AA, YK and AM designed the study. AA, AE and MA recruited the patients. AA, HA, MRG, WS, SC and DZ obtained the data. Amani Abderahmene performed the genotyping. DA performed the measurement of AUC0-12 MPA. AO and AA performed the statistical analysis and the interpretation of the data. AA wrote the manuscript. AO and DA provided a critical review of the manuscript.

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Correspondence to Amani Abderahmene.

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The pharmacogenetics of tacrolimus in renal transplant patients: Association with tremors, new-onset diabetes and other clinical events

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Abderahmene, A., khalij, Y., Moussa, A. et al. The pharmacogenetics of tacrolimus in renal transplant patients: association with tremors, new-onset diabetes and other clinical events. Pharmacogenomics J 24, 3 (2024). https://doi.org/10.1038/s41397-024-00323-4

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