Evaluation of the influence of polymorphism in the gene encoding multidrug resistance protein 2 (Mrp2) in iron chelator toxicity profile Deferasirox.

• Grant number: 15/05780-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2015
• End date: May 31, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Sara Teresinha Olalla Saad
• Grantee: Caroline Cordeiro Barroso Braga
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 11/51959-0 - Biology of neoplastic diseases of bone marrow, AP.TEM

Abstract

Regular blood transfusions are part of the treatment of several diseases such as hemoglobinopathies and myelodysplastic syndromes. Although it is indisputable the benefit of blood transfusions in these patients, this therapy can result in damage to various organs, resulting in Transfusion-Induced Iron Overload. In order to reverse and reduce the related complications of iron overload, it is necessary the use of iron chelating therapy. The deferasirox (Exjade) is the newest oral iron cheater administered as a single dose and have demonstrated good efficacy in the control of iron overload in these patients. Toxicity to deferasirox mainly include skin rash, nausea and diarrhea. However, the occurrence of changes in renal and liver function are also reported, including some rare cases of more serious complications such as liver failure. Being deferasirox metabolized by lucuronidation and eliminated into the bile justifies the study of genetic variability in enzymes involved in intestinal drug absorption and its hepatic elimination, such as MRP2 (multidrug resistance protein 2). The objective of this study is to evaluate the prevalence of genetic variants of MRP2 enzyme associated with the metabolism of this drug in patients treated at the Blood Center at Unicamp and its relation to adverse toxic effects occurring during use.