Estudo da relação entre o polimorfismo c.98T>C do gene UGT1A9 e níveis plasmáticos de ácido micofenólico em pacientes transplantados renais

• Ano de defesa: 2015
• Autor(a) principal: Ruschel , Lizania Rodrigues
• Orientador(a): Thiesen , Flavia Valladão
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Pontifícia Universidade Católica do Rio Grande do Sul
• Programa de Pós-Graduação: Programa de Pós-Graduação em Biotecnologia Farmacêutica
• Departamento: Faculdade de Farmácia
• País: Brasil
• Palavras-chave em Português: FARMACOLOGIA; BIOTECNOLOGIA - FÁRMACOS; PREPARAÇÕES FARMACÊUTICAS; FARMACOGENÉTICA; RINS - TRANSPLANTE
• Área do conhecimento CNPq: CIENCIAS DA SAUDE::FARMACIA
• Link de acesso: http://tede2.pucrs.br/tede2/handle/tede/6357

After the proceeding of a transplant, it is of huge concem the use of all therapeutic resource available in order to prevent graft rejection. The incidence and severity of acute rejection have been reduced along time due to the development of new immunosuppressive agents such as cyclosporin, tacrolimus, mycophenolate mofetil (MMF), specific polyclonal and monoclonal antibodies. Mofetil mycophenolate (MMF) is a prodrug active only after its hydrolysis to mycophenolic acid (MPA). Once it, has a large variability on inter-individual response, an increasing need of therapeutic monitoring arises. This will permit an individualization of MMF therapy, optimizing immunosuppression and minimizing potential toxic effects.The aim of pharmacogenetics is to evaluate the association between individual genetic characteristics and different responses to the same therapeutic regimen. When considering immunosuppressive drugs, genetic changes on a single nucleotide (single nucleotide polymorphisms - SNPs) of genes encoding proteins involved in transport or drug metabolism may affect patient’s response to therapy. UDP-glucuronosyltransferases (UGTs) belong to a group of enzymes involved in phase II reactions, responsible for the detoxification of endogenous and exogenous substrates. UGT1A9 is of particular interest once it is the primary enzyme involved in the metabolism of the MPA. This enzyme is encoded by the UGT1A9 gene.In the present study, we investigated the effect of UGT1A9 c.98T>C (rs72551330; g. 87289T>C) allelic variants on MMF metabolism in 39 renal transplant volunteers. MPA levels were measured by high pressure liquid chromatography using ultraviolet detection (HPLC/UV). The analysis of c.98T>C polymorphism was performed by polymerase chain reaction (PCR), followed by fragment purification and sequencing. All investigated individuals showed having the same polymorphism genotype (c.98TT) evaluation of variants or genotype influence on plasma levels of MPA and MPAG was not possible, even though different levels were observed in the study.