Study of expression and polymorphisms of MTOR, PPP3CA and PPP3CB genes in renal transplant recipients undergoing immunosuppressive therapy

• Grant number: 10/03463-3
• Support type: Scholarships in Brazil - Master
• Effective date (Start): August 01, 2010
• Effective date (End): February 29, 2012
• Field of knowledge: Health Sciences - Pharmacy
• Principal researcher: Rosario Dominguez Crespo Hirata
• Grantee: Patricia de Cássia Salgado
• Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Calcineurin inhibitors such as tacrolimus are used in the treatment of renal transplant recipients to prevent acute rejection. Prolonged use of this drug can result in side effects that contribute to decreased survival of the transplanted kidney. In order to avoid this outcome studies suggest the conversion to sirolimus therapy. However, the molecular mechanisms involved in the response to these drugs are not fully elucidated. The aim of this study is to investigate the relationship of polymorphisms of MTOR, PPP3CA, PPP3CB genes and the response to the imunossupressive and gene expression in peripheral blood leukocytes of renal transplant recipients. Two-hundred individuals undergoing renal transplant, of both sexes, aged over 18 and any ethinics. Will be recruited among patients treated at the Hospital do Rim e Hipertensão, UNIFESP. These patients will be treated with immunosuppressive therapy containing tacrolimus during 3 months and sirolimus after this period. Pharmacotherapy will be monitored by kidney function parameters and plasma concentration of imunossupressive drugs. Polymorphisms and gene expression will be evaluated by real time PCR. The results from this study will contribute to the knowledge of the pharmacogenomic mechanisms involved in response to immunosuppressive used in kidney transplantation and its relationship with graft rejection.