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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
11:06

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

An exploratory study on pharmacogenetics of inosine-monophosphate dehydrogenase II in peripheral mononuclear cells

F Vannozzi1, F Filipponi, A Di Paolo

  • 1Division of Pharmacology and Chemotherapy, Department of Oncology, Transplants and Advanced Technologies in Medicine, University of Pisa, 56126 Pisa, Italy.

Transplantation Proceedings
|December 29, 2004
PubMed

Insights

This study shows that measuring inosine-monophosphate dehydrogenase II (IMPDH II) gene expression using real-time PCR is feasible in liver transplant patients. Higher IMPDH II levels may correlate with mycophenolate mofetil (MMF) drug toxicity.

Area of Science:

  • Pharmacogenomics
  • Transplantation Immunology
  • Molecular Diagnostics

Background:

  • Mycophenolate mofetil (MMF) is a key immunosuppressant for preventing organ transplant rejection.
  • MMF's active metabolite, mycophenolic acid (MPA), inhibits inosine-monophosphate dehydrogenase II (IMPDH II), crucial for lymphocyte purine synthesis.
  • Assessing IMPDH II gene expression could offer insights into MMF efficacy and tolerability.

Purpose of the Study:

  • To assess the feasibility of quantifying IMPDH II gene expression in liver transplant recipients using real-time PCR.
  • To explore potential correlations between IMPDH II gene expression levels and MMF drug tolerability.
  • To investigate the utility of pharmacogenetic analysis for MMF therapeutic monitoring.

Main Methods:

  • Peripheral blood mononuclear cells (PBMCs) were collected from liver transplant recipients on MMF therapy.
  • Quantitative real-time PCR was employed to measure IMPDH II gene expression.
  • Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used for normalization, and adverse events were recorded.

Main Results:

  • Real-time PCR quantification of IMPDH II gene expression proved reliable, sensitive, and specific.
  • Low intrapatient variability (<0.6%) was observed for both IMPDH II and GAPDH assays.
  • Significant interpatient variability in IMPDH II expression was noted, with a trend towards higher expression in patients experiencing MMF-related toxicities.

Conclusions:

  • Quantitative real-time PCR is a feasible method for assessing IMPDH II gene expression in liver transplant recipients.
  • IMPDH II gene expression levels may serve as a potential biomarker for MMF tolerability.
  • Pharmacogenetic analysis of IMPDH II offers a novel avenue for optimizing MMF therapeutic monitoring in transplant patients.

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