Polimorfismos GSTM1, GSTT1 e GSTP1 da enzima Glutationa S-transferase como fatores moduladores do fenótipo na anemia falciforme

• Ano de defesa: 2014
• Autor(a) principal: Barberino, Willian Marcel [UNESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Estadual Paulista (Unesp)
• Palavras-chave em Português: Genética molecular humana; Anemia falciforme - Aspectos genéticos; Polimorfismo (Genetica); Glutationa transferase; Stress oxidativo; Dano ao DNA; Human molecular genetics
• Link de acesso: http://hdl.handle.net/11449/122180

Sickle cell anemia (SCA) is an inherited hemolytic disease that leads complex and diverse clinical manifestations. In SCA, oxidative stress is one of the factors that affect the phenotype of the carrier, in response of its influences on vaso-occlusion processes that increases the adhesive properties of erythrocytes, leukocytes and platelets to the endothelium. During the transformation of discoid erythrocytes with hemoglobin (Hb) S into sickle cells, among the biochemical and polymerizing events, the oxidative degradation of this Hb occurs, releasing pro-oxidants agents. They promote oxidation of lipids and proteins and modify cellular mechanisms that lead to cell apoptosis and cause tissue damage. In this context, the main means of body defense are divided in two groups: enzymatic and non-enzymatic. Among the phase II detoxifying enzymes, the most studied are Glutathione S-transferases (GSTs), which belong to a family of multifunctional enzymes that catalyze the combination of the glutathione (GSH) molecule and have a central role in mechanisms of defense against xenobiotic compounds. Considering the high incidence of SCA in our country and the different clinical manifestations in patients, this study aimed to investigate polymorphisms of GSTs (GSTM1 , GSTT1 and GSTP1 ) and determine its influence on oxidative parameters - lipid peroxidation by TBARS and DNA damage by evaluation of Howell -Jolly bodies (HJB) and comet assay in patients with SCA. Samples of 91 patients with SCA with and without hydroxyurea (HU) use and 99 samples of a control group were evaluated. For the work development, the samples were separated into three groups: individuals with sickle cell anemia using hydroxyurea (SCA + HU: 46 individuals), individuals with sickle cell disease without use of hydroxyurea (SCA - HU: 45 individuals) and control group (CG: 99 individuals) to verify the influence of medication on the evaluated parameters. Only the genotypic profile ...