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

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.