Pharmacogenetics of mycophenolate mofetil: a promising different approach to tailoring immunosuppression?
Since the Human Genome Project, the evaluation of the effectiveness and safety of some medications has become partially connected to innate metabolic patterns. Thus, genes that encode receptors and enzymes could play different roles in metabolism, according to their polymorphisms. Especially in organ transplantation, some of the available medications used in immunosuppressive therapy have a narrow therapeutic index, affecting the individual response to these drugs. This review focuses on the polymorphism of genes that encode enzymes of the uridino-glucuronosyltransferase (UGT) family, responsible for the bioavailability of mycophenolic acid, the active metabolite of mycophenolate mofetil (MMF), used as an immunosuppressant in solid organ transplantation. The increasing literature data regarding the pharmacogenetics of UGT and MMF suggest that enzyme polymorphism can explain the factors which influence the occurrence of side effects in patients receiving MMF as drug transplant therapy.
Betonico
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Genetics and Molecular Biology Research Unit - UPGEM, Sao Jose' do Rio Preto Medical School (FAMERP), Sao Jose' do Rio Preto, Sao Paulo - Brazil.
Abudd-Filho
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Goloni-Bertollo
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EM
Pavarino-Bertelli
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D004247:DNA / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016377:Organ Transplantation; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011355:Prodrugs
D007166:Immunosuppressive Agents; D011355:Prodrugs; D004247:DNA; D014453:Glucuronosyltransferase; D009173:Mycophenolic Acid