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Polymorphism of the hemopexin (hpx) gene in sickle cell anemia

Grant number: 13/22553-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2014
Effective date (End): May 31, 2015
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal researcher:Maria de Fatima Sonati
Grantee:Ligia Maria Sotero Machado
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Sickle cell anemia (SCA) is the most prevalent genetic disorder in Brazilian population, presenting an exceptional phenotypic heterogeneity that is probably the result of the effect of multiple genetic and environmental modifiers. The inflammatory phenomena is the determinant pathophysiological event in the origin of the great majority of signs and symptoms presents in the clinical manifestation of SCA, that has been characterized as a chronic inflammatory state with abnormal endothelial activation. The actual process of intravascular hemolysis, with the release of hemoglobin (Hb) contained in erythrocytes, is an important mediator in vascular diseases. The toxicity and inflammatory nature of free Hb are a result of the greater nitric oxide consumption it promotes and the consequent accumulation of hydroxyl radicals and reactive oxygen species in the blood vessels. In addition to the protection against the harmful effects of free Hb afforded by haptoglobin, protection is also provided by hemopexin (Hpx), a plasma glycoprotein whose primary function is to bind to the heme group and transport it to the liver where it is broken down so that the iron can be re-used to synthesize other proteins, thereby also protecting blood vessels from heme-mediated oxidative stress. The Hpx molecule consists of a long polypeptide chain made up of 439 amino acids that is encoded by the HPX gene, which is located on the short arm of chromosome 11 (11p15.5-p15.4). Although , Hpx have its structure and functions extensively studied, little is known about its polymorphism , which is believed to have biological significance in patients with hemolytic disorders such as SCA. The aim of this study is to determine the polymorphisms of the HPX gene using DNA samples from patients with SCA, followed in Pernambuco´s Blood Center -HEMOPE, in an attempt to assess the role of these polymorphisms and to contribute to a better understanding of the inflammatory state in these patients. The polymorphisms will be determined by means of a strategy using genetic sequencing.