Presence of the polymorphism 313A>G of GSTP1 and response to treatment with hydroxyurea in sickle cell anemia

• Grant number: 12/04768-8
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2012
• Effective date (End): December 31, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Claudia Regina Bonini Domingos
• Grantee: Renan Garcia de Oliveira
• Home Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

The Sickle Cell Anemia (SCA) is the most common monogenic hereditary disease, occurring predominantly among African Americans and has a heterogeneous distribution. Occurs due the mutation in the sixth codon of the beta globin gene (GAG’ GTG), which results in the substitution of glutamic acid for valine, in beta globin chain, resulting in the hemoglobin (Hb) S, with physico-chemical features. Under specific conditions like hypoxia, dehydration or acidosis, the Hb S polymerizes and triggers the first event the essential molecular pathogenesis of SCA. This polymerization within the erythrocyte, has as a consequence, multiple cell changes as efflux of monovalent ions, cellular dehydration, increased of density, hemoglobin oxidation, hemolysis and Hb denaturation. Recent studies have revealed that the pathophysiology of SCA is complex and recurrent processes of vaso-occlusion, leukocyte and endothelial activation cells, induction of inflammatory mediators, decreased bioavailability of nitric oxide (NO) and oxidative stress. The use of hydroxyurea (HU) has been an alternative to the treatment of SCA for inducing an increase in Hb F synthesis, increase of the Hb rate and mean corpuscular volume (MCV), reduce the number of reticulocytes, the expression of adhesion molecules, the number of granulocytes, monocytes and platelets. However, not all patients respond to treatment with HU. Whereas the HU is a drug used to treat SCA which did not meet responses to the laboratory and clinical parameters for all patients, and the polymorphism 313A>G of the GSTP1 is involved in the differential response to chemotherapy treatment of other diseases, we aimed to assess the influence of polymorphism 313A> G of GSTP1 gene in subjects with sickle cell anemia in the use of HU, without the interference of the GSTM1 and GSTT1 polymorphisms, through biochemical parameters such as the quantification of MDA (malondialdehyde),the activity profile of GST, GPx and determine the levels of GSH / GSSG ratio compared with the control group.