Pharmacogenetics of Mycophenolic Acid in Patients of African Descent: Underrepresentation of African Data.

Migael Mouton, Bianca Davidson, Jessica Taylor, Marc Blockman, Erika Jones, Robert Freercks, Khuthala Mnika, Collet Dandara

Journal: Clinical and translational science 2026;19(5):e70599

PMID: 42137999

Abstract

Mycophenolic acid (MPA) is a potent antiproliferative immunosuppressive agent used to prevent organ transplant rejection and to treat various immune-mediated diseases. MPA is the active metabolite formed from the biotransformation of the prodrugs mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). MPA exerts its therapeutic effects by inhibiting guanosine nucleotide synthesis in lymphocytes. Through this inhibition, cell and humoral immunity is suppressed, resulting in a reduction of cytotoxicity and inflammation. Systemic exposure to MPA is influenced by a complex pharmacokinetic pathway, which involves various drug-metabolizing enzymes (DMEs) and transporters. Substantial interindividual variability exists in MPA exposure, efficacy, and adverse effects. Genetic polymorphisms in the genes encoding DMEs and transporters have been reported to influence this observed variability; however, evidence remains inconsistent and is largely derived from non-African populations. African populations exhibit high levels of genetic diversity, and their underrepresentation in pharmacogenetic studies may hinder the identification of important variants influencing MPA disposition and clinical outcomes. This review evaluates the genes that have been reported to affect MPA exposure as well as highlights conflicting results on the role of these pharmacogenetic variants in different populations. The review highlights the lack of data on African populations and provides justification for their inclusion in the study of MPA pharmacogenetics.

© 2026 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

Address: Division of Human Genetics, Department of Pathology and Institute of Infectious Disease and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; SAMRC/UCT Platform for Pharmacogenomics Research and Translation, South African Medical Research Council, Cape Town, South Africa.; SAMRC/UCT Platform for Pharmacogenomics Research and Translation, South African Medical Research Council, Cape Town, South Africa.; Division of Nephrology and Hypertension, Department of Medicine, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Division of Clinical Pharmacology, Department of Medicine, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; Faculty of Health Sciences, Department of Medicine, Nelson Mandela University, Gqeberha, South Africa.

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