Pharmacogenomics of mycophenolic acid in kidney transplantation

Contribution of immune response-related genes

Authors

  • Rosario Dominguez Crespo Hirata Department of Clinical & Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil https://orcid.org/0000-0003-3073-5967
  • Fabiana Dalla Vecchia Genvigir Department of Clinical & Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil
  • Thiago Dominguez Crespo Hirata Department of Clinical & Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil
  • Alvaro Cerda Department of Basic Sciences https://orcid.org/0000-0003-3428-8332
  • Mario Hiroyuki Hirata Department of Clinical & Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil

DOI:

https://doi.org/10.1590/s2175-97902022e201188

Keywords:

Immunosuppressive therapy, Mycophenolic acid, Kidney transplantation, Pharmacogenomics, Immune response

Abstract

Mycophenolic acid (MPA) inhibits IMPDH, involved in the guanosine nucleotides synthesis, and prevents DNA replication in immune cells. The repression of cell and humoral immunity by MPA induces allograft tolerance preventing acute rejection in solid organ transplantation. MPA is an effective and safe drug, but genetic and non-genetic factors have been implicated in the interindividual variability of drug response. Several studies have shown the impact of variants of pharmacokinetics or pharmacodynamics-related genes on MPA response in kidney transplantation. This review explored further the influence of genes involved in the immune response on clinical outcomes of kidney recipients on short- or long-term MPA treatment. Variants in genes related to T cell activation (CD28CTL4ICOSPDPC1), pro-inflammatory cytokines (IL2, IL6, IL12A, IL12B, TNFIFNG), immunomodulatory cytokines (IL4, IL10, TGFB1), and innate immune response (CD14, TLR2, TLR4) were shown to be associated with increased risk of acute rejection, graft function or survival, chronic graft nephropathy, viral infections or MPA-induced myelotoxicity. Some of the significant pharmacogenetic associations were confirmed by meta-analyses of kidney transplantation. These findings are suggestive that variants in immune response-related genes contribute to the variability of MPA response, and have potential application as biomarkers of acute rejection in kidney transplantation.

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References

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Published

2023-02-06

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Review

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Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes. (2023). Brazilian Journal of Pharmaceutical Sciences, 58. https://doi.org/10.1590/s2175-97902022e201188