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

• Grant number: 11/10039-6
• Support Opportunities: Regular Research Grants
• Duration: September 01, 2011 - August 31, 2013
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Rosario Dominguez Crespo Hirata
• Grantee: Rosario Dominguez Crespo Hirata
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Alice Cristina Rodrigues ; Jose Osmar Medina de Abreu Pestana ; Mario Hiroyuki Hirata

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 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)

Scientific publications

(4)

(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)

BONEZI, VIVIAN; GENVIGIR, FABIANA DALLA VECCHIA; SALGADO, PATRICIA DE CASSIA; FELIPE, CLAUDIA ROSSO; TEDESCO-SILVA JR, HELIO; MEDINA-PESTANA, JOSE OSMAR; CERDA, ALVARO; DOI, SONIA QUATELI; HIRATA, MARIO HIROYUKI; CRESPO HIRATA, ROSARIO DOMINGUEZ. Differential expression of genes related to calcineurin and mTOR signaling and regulatory miRNAs in peripheral blood from kidney recipients under tacrolimus-based therapy. ANNALS OF TRANSLATIONAL MEDICINE, v. 8, n. 17, p. 14-pg., 2020-09-01. (11/10039-6, 16/13118-8)

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, OCT 2016. (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, MAY 2017. (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, 2017. (11/10039-6)