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

• Grant number: 11/14168-5
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2012
• Effective date (End): February 28, 2013
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Claudia Regina Bonini Domingos
• Grantee: Jéssika Viviani Okumura
• Host 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

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.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

OKUMURA, V, JESSIKA; SILVA, DANILO G. H.; TORRES, LIDIANE S.; BELINI-JUNIOR, EDIS; VENANCIO, LARISSA P. R.; CARROCINI, GISELE C. S.; NASCIMENTO, PATRICIA P.; LOBO, CLARISSE L. C.; BONINI-DOMINGOS, CLAUDIA R.. Atypical beta-S haplotypes: classification and genetic modulation in patients with sickle cell anemia. JOURNAL OF HUMAN GENETICS, v. 64, n. 3, p. 239-248, MAR 2019. (13/07937-8, 11/14168-5)

OKUMURA, JESSIKA V.; SILVA, DANILO G. H.; TORRES, LIDIANE S.; BELINI-JUNIOR, EDIS; BARBERINO, WILLIAN M.; OLIVEIRA, RENAN G.; CARROCINI, GISELE C. S.; GELALETI, GABRIELA B.; LOBO, CLARISSE L. C.; BONINI-DOMINGOS, CLAUDIA R.. Inheritance of the Bantu/Benin haplotype causes less severe hemolytic and oxidative stress in sickle cell anemia patients treated with hydroxycarbamide. JOURNAL OF HUMAN GENETICS, v. 61, n. 7, p. 605-611, JUL 2016. (11/14168-5)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

OKUMURA, Jéssika Viviani. Modulação pelo haplótipo Bantu da resposta ao uso de hidroxiureia em anemia falciforme. 2013. Master's Dissertation - Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto São José do Rio Preto.