Influence of UDP-glucuronosyltransferase polymorphisms on mycophenolate mofetil-induced side effects in kidney transplant patients

Transplant Proc. 2008 Apr;40(3):708-10. doi: 10.1016/j.transproceed.2008.03.007.

Abstract

Mycophenolate mofetil (MMF) is an immunosuppressive prodrug approved for use in transplantation. Its active metabolite, mycophenolic acid, is mainly metabolized by UDP-glucuronosyltransferase (UGT) enzymes. In this study, we retrospectively analyzed 74 kidney transplant patients who had been prescribed MMF as part of their immunosuppression regimen. Polymorphisms in UGT1A8 (-999C > T, codon 255A > G, codon 277G > A) were correlated with the occurrence of side effects, such as diarrhea, blood disorders, and infections. The infectious episodes were more frequently observed among individuals receiving MMF (2 g/d) who carryied the variant UGT1A8 codon 277A (P = .031), the haplotype UGT1A8H5 (-999C/codon 55A/codon 277A; P = .02), and the diplotype UGT1A8H2/H5 (-999CC/codon 255AA/codon 277GA; P = .015). The molecular data from this study suggest that UGT polymorphisms may be a factor influencing clinical outcomes among patients receiving MMF for transplant therapy; however, larger studies are warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Codon / genetics
  • Diarrhea / chemically induced
  • Glucuronosyltransferase / genetics*
  • Hematologic Diseases / chemically induced
  • Humans
  • Infections / epidemiology
  • Kidney Transplantation / immunology*
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives*
  • Polymorphism, Single Nucleotide*
  • Retrospective Studies

Substances

  • Codon
  • Glucuronosyltransferase
  • Mycophenolic Acid