Genetic polymorphisms and markers expression involved in inflammatory processes, angiogenesis and hypoxia in sickle cell disease

• Grant number: 12/19653-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2013
• End date: February 29, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Claudia Regina Bonini Domingos
• Grantee: Lidiane de Souza Torres
• 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 disease (SCD) is the term for hereditary anemias with presence of hemoglobin (Hb) S. It involves homozygous for Hb S (sickle cell anemia) and its association with other variants or thalassemia. The SCD is usually more severe in patients with Hb SS, followed by Hb S / beta-thalassemia, Hb SC and Hb SD, however, the clinical manifestations can be variable between individuals of the same genotype. The primary event responsible by the SCD complications is the polymerization of Hb S, followed by vascular occlusion, which corresponds to the main inflammatory stimulus of the disease and is associated with clinical complications such as vasculopathies. Several pro-inflammatory cytokines are elevated in the disease, and an exacerbated inflammatory response can result in tissue hypoxia and angiogenesis stimulation. Many studies are conducted about sickle cell anemia, but for other genotypes of DF the studies are scarce. The aim of this study is to analyze the processes of inflammation, angiogenesis and hypoxia in SCD - Hb SS, Hb S / beta-thalassemia, Hb SC and Hb D genotypes, aiming to understand the mechanisms that modulate the disease phenotype. We will evaluate pro-inflammatory markers (TNF-±, TGF-², IL-1² and IL-8), the anti-inflammatory (ANXA1) marker, angiogenic marker (VEGF) and hypoxia marker (HIF-1±), in these patients, comparing the results to a control group without hemoglobinopathies. Genetic polymorphisms in these markers will be analyzed by PCR-RFLP, while the plasma measurements will be performed by immunoassay in ELISA and multiplex analysis in Magpix technology. It is expected that polymorphisms screened contribute to the individual variations in plasma levels of biomarkers and it is possible to derive a relationship between the presence of these polymorphisms and the genotypes of SCD.

Scientific publications

(4)

(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)

TORRES, LIDIANE DE SOUZA; OKUMURA, JESSIKA VIVIANI; HUMBERTO DA SILVA, DANILO GRUNIG; BELINI JUNIOR, EDIS; DE OLIVEIRA, RENAN GARCIA; OLIVEIRA MIMURA, KALLYNE KIOKO; DE CASTRO LOBO, CLARISSE LOPES; OLIANI, SONIA MARIA; BONINI DOMINGOS, CLAUDIA REGINA. Plasma levels of TGF-beta 1 in homeostasis of the inflammation in sickle cell disease. CYTOKINE, v. 80, p. 18-25, APR 2016. (12/19653-1)

TORRES, LIDIANE S.; OKUMURA, JESSIKA V.; BELINI-JUNIOR, EDIS; OLIVEIRA, RENAN G.; NASCIMENTO, PATRICIA P.; SILVA, DANILO G. H.; LOBO, CLARISSE L. C.; OLIANI, SONIA M.; BONINI-DOMINGOS, CLAUDIA R.. Phenotypic Diversity of Sickle Cell Disease in Patients with a Double Heterozygosity for Hb S and Hb D-Punjab. HEMOGLOBIN, v. 40, n. 5, p. 356-358, SEP 2016. (12/19653-1)

TORRES, LIDIANE S.; OKUMURA, JESSIKA V.; SILVA, DANILO G. H.; MIMURA, KALLYNE K. O.; BELINI-JUNIOR, EDIS; OLIVEIRA, RENAN G.; LOBO, CLARISSE L. C.; OLIANI, SONIA M.; BONINI-DOMINGOS, CLAUDIA R.. Inflammation in Sickle Cell Disease: Differential and Down-Expressed Plasma Levels of Annexin A1 Protein. PLoS One, v. 11, n. 11, NOV 1 2016. (12/21603-2, 12/19653-1)

TORRES, LIDIANE S.; OKUMURA, JESSIKA V.; SILVA, DANILO G. H.; MIMURA, KALLYNE K. O.; BELINI-JUNIOR, EDIS; OLIVEIRA, RENAN G.; LOBO, CLARISSE L. C.; OLIANI, SONIA M.; BONINI-DOMINGOS, CLAUDIA R.. Inflammation in Sickle Cell Disease: Differential and Down-Expressed Plasma Levels of Annexin A1 Protein (vol 11, e0165833, 2016). PLoS One, v. 12, n. 2, p. 1-pg., 2017-02-16. (12/19653-1, 12/21603-2, 16/22239-3)

Academic Publications

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

TORRES, Lidiane de Souza. Genetic polymorphisms and expression of markers involved in inflammatory, angiogenic and hypoxic processes in sickle cell disease. 2016. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto São José do Rio Preto.