Bantu haplotype modulation of the response to the hydroxyurea usage in sickle cell anemia

Abstract

Sickle cell anemia (SCA) features complex pathophysiology and is characterized by the polymerization of hemoglobin (Hb) S and consequent hemolysis, vascular occlusion, oxidative stress and increased medullary request. These pathophysiologic processes difficult the treatment and culminate in the development of diverse clinical manifestations that are modulated by genetic and biochemical markers, including the Beta-S-globin gene cluster (²S) haplotypes, co-inheritance of polymorphisms involved in its pathophysiology, and chronic inflammation and oxidative states. Among the mechanisms for oxidative controlling, there are detoxified pathways that are mediated by haptoglobin and hemopexin proteins, which form complexes with free Hb and heme, respectively, ensuring antioxidant and anti-inflammatory effects. The SCA epidemiological significance, its complex and diverse pathophysiological processes, which complicate treatment and trigger to varied clinical manifestations, make this genetic disorder a public health problem in Brazil. These features justify the importance of this study that aims, in SCA patients, to characterize ²S haplotypes and evaluate their association with biochemical and hematological markers linked to SCA pathophysiology, for better understanding of individual response to the treatment with hydroxyurea.