Frequency of polymorphism rs3800231 in the FOXO3 gene and its relation with markers of oxidative stress in individuals with sickle cell disease: a comparison with clinical severity

• Grant number: 18/00345-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2018
• End date: February 28, 2019
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Claudia Regina Bonini Domingos
• Grantee: Victoria Simões Bernardo
• 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

Hemoglobinopathies are inherited hematological diseases of monogenic origin and autosomal recessive transmission. The term sickle disease (SCD) is used to represent a group of genetic disorders characterized by the presence of HbS, either in homozygosis, characterized by sickle cell anemia (SCA) recognized as the condition of greatest clinical significance within the group, or by its presence in heterozygous compound with other Hb variants such as SC and SD and association with thalassemia such as S/beta thalassemia. SCD affects millions of people worldwide and leads to severe clinical conditions and high morbidity. The FOXO3 gene encodes a protein of the same name, which controls the transcription of several crucial genes for the regulation of a wide variety of biological processes, for example, its role as a positive regulator for apoptosis by BIM and FasL genes, or the regulation of oxidative stress in hematopoietic stem cells with the regulation of Catalase, among others. It is therefore considered a potential target for treatment of several types of diseases. Recent studies have reported that changes in this gene in clinical cases that result in abnormal hematopoiesis. It is therefore assumed that mutations presented in this sequence possibly lead to modifications of the clinical manifestations of individuals whom have SCD. The aim of this study is to verify the genotypic and allelic frequency of rs3800231 polymorphism in the FOXO3 gene in adults and children with HbS, and to correlate the polymorphism with oxidative stress markers and clinical severity in a group of adults with sickle cell disease (SS, SC, SD, S²). In addition, a control group will be used to compare the frequency of polymorphism and values of oxidative stress markers with the study group. For the characterization of polymorphism rs3800231 will be used PCR-RFLP; the antioxidant capacity will be evaluated by lipid peroxidation measured by thiobarbituric acid reactive species (TBARS) and catalase activity, and gravity will be characterized by the use of the Sickle Cell Disease Severity Calculator. According to the action of the FOXO3 gene and because there is no study to evaluate its polymorphisms with SCD, this work is of great importance, since it will report the frequency of rs3800231 polymorphism in Brazilian individuals who present this hemoglobinopathy and will relate to antioxidant capacity markers and clinical severity in these individuals.

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)

BERNARDO, VICTORIA SIMOES; TORRES, FLAVIENE FELIX; CHAVES, NAYARA ALVES; OKUMURA, JESSIKA VIVIANI; HUMBERTO DA SILVA, DANILO GRUNIG; BONINI-DOMINGOS, CLAUDIA REGINA. Relationship of polymorphism rs3800231 in FOXO3 gene and clinical severity with oxidative stress markers in sickle cell disease. META GENE, v. 24, JUN 2020. (18/00345-1)