Influence of UDP-glucuronosyltransferase polymorphisms on mycophenolate mofetil-induced side effects in kidney transplant patients.
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.
Betônico
G N
GN
Genetics and Molecular Biology Research Unit-UPGEM, São José do Rio Preto School of Medicine, FAMERP, São José do Rio Preto, Brazil.
Abbud-Filho
M
M
Goloni-Bertollo
E M
EM
Alvarenga
M P S
MP
Guillemette
C
C
Villeneuve
L
L
Benoit-Biancamano
M-O
MO
Pavarino-Bertelli
E C
EC
D003062:Codon / Q000235:genetics; D003967:Diarrhea / Q000139:chemically induced; D014453:Glucuronosyltransferase / Q000235:genetics*; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007239:Infections / Q000453:epidemiology; D016030:Kidney Transplantation / Q000276:immunology*; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies
D003062:Codon; D014453:Glucuronosyltransferase; D009173:Mycophenolic Acid