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

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.

• Authors: G N Betônico, M Abbud-Filho, E M Goloni-Bertollo, M P S Alvarenga, C Guillemette, L Villeneuve, M-O Benoit-Biancamano, E C Pavarino-Bertelli
• Journal: Transplantation proceedings (Transplant Proc) Vol. 40 Issue 3 Pg. 708-10 (Apr 2008) ISSN: 0041-1345 [Print] United States
• PMID: 18454993 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Codon
• Glucuronosyltransferase
• Mycophenolic Acid

Topics

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