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Study of the expression and candidate gene polymorphisms of calcineurin inhibitors in renal transplant recipients


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 calcineurin inhibitors gene polymorphisms (MTOR, PPP3CA, PPP3CB) with the response to the immunosuppressive drugs and with gene expression in peripheral blood leukocytes from 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. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GENVIGIR, FABIANA D. V.; SALGADO, PATRICIA C.; FELIPE, CLAUDIA R.; LUO, ELENA Y. F.; ALVES, CAMILA; CERDA, ALVARO; TEDESCO-SILVA, JR., HELIO; MEDINA-PESTANA, JOSE O.; OLIVEIRA, NAGILLA; RODRIGUES, ALICE C.; et al. Influence of the CYP3A4/5 genetic score and ABCB1 polymorphisms on tacrolimus exposure and renal function in Brazilian kidney transplant patients. PHARMACOGENETICS AND GENOMICS, v. 26, n. 10, p. 462-472, . (11/10039-6)
GENVIGIR, FABIANA D. V.; NISHIKAWA, ALVARO M.; FELIPE, CLAUDIA R.; TEDESCO-SILVA, JR., HELIO; OLIVEIRA, NAGILLA; SALAZAR, ANTONY B. C.; MEDINA-PESTANA, JOSE O.; DOI, SONIA Q.; HIRATA, MARIO H.; HIRATA, ROSARIO D. C.. Influence of ABCC2, CYP2C8, and CYP2J2 Polymorphisms on Tacrolimus and Mycophenolate Sodium-Based Treatment in Brazilian Kidney Transplant Recipients. PHARMACOTHERAPY, v. 37, n. 5, p. 535-545, . (11/10039-6, 16/13118-8)
SALGADO, PATRICIA C.; GENVIGIR, FABIANA D. V.; FELIPE, CLAUDIA R.; TEDESCO-SILVA, JR., HELIO; MEDINA-PESTANA, JOSE O.; DOI, SONIA Q.; HIRATA, MARIO H.; HIRATA, ROSARIO D. C.. Association of the PPP3CA c.249G>A variant with clinical outcomes of tacrolimus-based therapy in kidney transplant recipients. PHARMACOGENOMICS & PERSONALIZED MEDICINE, v. 10, p. 101-105, . (11/10039-6)

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