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Inosine monophosphate dehydrogenase type 2 polymorphism IMPDH2 3757T>C (rs11706052) and 12-month evolution of the graft function in renal transplant recipients on mycophenolate-based immunosuppression

The Pharmacogenomics Journal volume 24, Article number: 15 (2024) Cite this article

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Abstract

Variant allele at the inosine monophosphate dehydrogenase type 2 polymorphism IMPDH2 3757T>C has been associated with increased enzyme activity and reduced susceptibility to mycophenolic acid (MPA) in vitro. It has been suggested associated with an increased risk of acute rejection in renal transplant recipients on MPA-based immunosuppression, but not unambiguously. We assessed one-year evolution of the estimated glomerular filtration rate (eGFR) in transplanted variant allele carriers and wild-type subjects, while controlling for a number of demographic, pharmacogenetic, (co)morbidity, and treatment baseline and time-varying covariates. The eGFR slopes to day 28 (GMR = 1.01, 95% CI 0.93–1.09), and between days 28 and 365 (GMR = 1.01, 95% CI 0.99–1.02) were practically identical in 52 variant carriers and 202 wild-type controls. The estimates (95%CIs) remained within the limits of ±20% difference even after adjustment for a strong hypothetical effect of unmeasured confounders. Polymorphism IMPDH2 3757T>C does not affect the renal graft function over the 1st year after transplantation.

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Fig. 1: Schematic representation of the assessment of the primary outcome.
Fig. 2: Primary study outcome in the adjusted analysis.

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Data availability

Data collected and analyzed in this work are avaialbe from the corresponding authors upon a reasonable request.

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Acknowledgements

The authors thank Mrs Zrinka Mirković and Mrs Maja Mezak Herceg for technical assistance during genotyping procedures.

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Authors and Affiliations

  1. Department of Urology, University Hospital Center Zagreb, Zagreb, Croatia

    Luka Penezić, Sandra Nađ-Škegro & Željko Kaštelan

  2. Teaching Institute for Emergency Medicine of Istria County, Zagreb, Croatia

    Ayla Hadžavdić

  3. Division of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia

    Lana Ganoci

  4. Department of Urology, University of Zagreb School of Medicine, Zagreb, Croatia

    Željko Kaštelan

  5. Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia

    Vladimir Trkulja & Nada Božina

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  1. Luka Penezić
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Contributions

LP, SNŠ, NB, and ŽK were the principal investigators and provided the conception and design of the study. LP, SNŠ, AH and LG acquired the clinical and laboratory data. NB supervised the genetic analysis. VT contributed to study design. VT and NB analyzed and interpreted the data, and drafted the manuscript. All authors reviewed the manuscript and approved it for publication.

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Correspondence to Vladimir Trkulja.

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Penezić, L., Nađ-Škegro, S., Hadžavdić, A. et al. Inosine monophosphate dehydrogenase type 2 polymorphism IMPDH2 3757T>C (rs11706052) and 12-month evolution of the graft function in renal transplant recipients on mycophenolate-based immunosuppression. Pharmacogenomics J 24, 15 (2024). https://doi.org/10.1038/s41397-024-00335-0

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