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Genvigir et al. J Transl Genet Genom 2020;4:320-55 Journal of Translational
DOI: 10.20517/jtgg.2020.37 Genetics and Genomics

Review Open Access

Mycophenolic acid pharmacogenomics in kidney
transplantation

Fabiana Dalla Vecchia Genvigir , Alvaro Cerda , Thiago Dominguez Crespo Hirata , Mario Hiroyuki Hirata ,
2
1
1
1
Rosario Dominguez Crespo Hirata 1
1 Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo
05508-000, Brazil.
2 Department of Basic Sciences, Center of Excellence in Translational Medicine, CEMT-BIOREN, Universidad de La Frontera,
Temuco 4810296, Chile.
Correspondence to: Prof. Rosario Dominguez Crespo Hirata, Department of Clinical and Toxicological Analyses, School of
Pharmaceutical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes 580, Sao Paulo 05508-000, Brazil.
E-mail: rosariohirata@usp.br
How to cite this article: Genvigir FDV, Cerda A, Hirata TDC, Hirata MH, Hirata RDC. Mycophenolic acid pharmacogenomics in
kidney transplantation. J Transl Genet Genom 2020;4:320-55. http://dx.doi.org/10.20517/jtgg.2020.37
Received: 12 Jun 2020 First Decision: 23 Jul 2020 Revised: 30 Jul 2020 Accepted: 17 Aug 2020 Available online: 28 Aug 2020

Academic Editor: Ramón Cacabelos Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Mycophenolic acid (MPA) is a potent antiproliferative drug prescribed to prevent acute rejection in kidney
transplantation. MPA reversibly inhibits the enzymes involved in the synthesis of guanosine nucleotides, thus
preventing DNA replication of immune cells. Consequently, the repression of both cell and humoral immunity
induces renal allograft tolerance. MPA is an effective and safe immunosuppressive drug, but some patients show
variability in drug concentration, acute rejection, graft dysfunction, or MPA-related adverse events. Although
the pharmacogenomics of immunosuppressive drugs has been widely investigated, MPA has been explored
to a lesser extent. This review of MPA pharmacogenomic studies, included pharmacokinetics, adverse events,
and main clinical outcomes of MPA treatment in kidney transplantation. Associations of variants in genes
encoding MPA metabolizing enzymes, transporters, and targets with drug efficacy and safety are described.
Most pharmacogenetic studies have focused on small sample sizes and few simultaneously analyzed genetic
variants. Some studies reported significant associations of pharmacokinetics- and pharmacodynamics-related
genes with MPA exposure, acute rejection, graft dysfunction, hematological events, and gastrointestinal
complications. However, even large cohorts did not replicate the findings, possibly due to divergent study design,
immunosuppressive scheme, follow-up time, and other factors. Finally, the heterogeneity of aspects between
studies limit conclusions on pharmacogenetic biomarkers of MPA in kidney transplantation.

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
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