Influence of Genetic Polymorphisms on Mycophenolic Acid Pharmacokinetics and Patient Outcomes in Renal Transplantation

Background: Mycophenolic Acid (MPA) is an immunosuppressive drug widely used in the treatment of organ transplantation and autoimmune diseases. Pharmacokinetics and pharmacodynamics of MPA varies between individuals, the potential reasons being the genetic polymorphisms in key enzymes, drug transporters and target proteins of MPA.

Objective: We try to provide pharmacogenomics information for drug selection and dose adjustment, aiming to improve drug efficacy and reduce side effects in clinical application of MPA.

Methods: In this review, we summarize the literatures in Pubmed that reported MPA-related Single Nucleotide Polymorphisms (SNPs) of renal transplant patients in recent 15 years.

Results: Genetic polymorphisms involving uridine diphosphate glucuronosyltransferase enzymes, organic anion transport polypeptides, multidrug resistance-associated protein 2, inosine monophosphate dehydrogenase and immune- response mediators may be associated with the metabolism, efficacy and toxicity of MPA, thus resulting in different MPA exposure and patient outcomes in renal transplantation.

Conclusion: Several SNPs show significant association with MPA pharmacokinetics and pharmacodynamics, but conflicting results are reported, and no studies on MPA genetic polymorphisms have been translated into clinical practice. More prospective studies are needed to clear the role of genetic polymorphisms on MPA in renal transplantation patients.