Evaluation of Genes and Molecular Pathways Involved in  Pathogenesis of Sickle Cell Anemia: A Bioinformatics Analysis and Future Perspective

Reza  Maddah; Sareh  Etemad; Bahareh Shateri  Amiri; Hajarossadat  Ghaderi; Hamidreza Zarei; Ferdos  Faghihkhorasani; Hadi Rezaeeyan

doi:10.18502/ijph.v53i6.15914

Reza Maddah Department of Bioprocess Engineering, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic En-gineering and Biotechnology, Tehran, Iran
Sareh Etemad Department of Pathology, Faculty of Anatomical Pathology Ghaem Hospital, University of Medicine, Mashhad, Iran
Bahareh Shateri Amiri Department of Internal Medicine, School of Medicine Hazrat-e Rasool General Hospital, Iran University of Medical Sciences, Teh-ran, Iran
Hajarossadat Ghaderi Laboratory of Regenerative and Medical Innovation, Pasteur Institute of Iran, Tehran, Iran
Hamidreza Zarei Department of Internal Medicine, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Ferdos Faghihkhorasani Medical Campus, Xian Jiaotong University, Xian, Shaanxi Province, China
Hadi Rezaeeyan Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Iranian Blood Transfu-sion Organization (IBTO), Tehran, Iran

DOI: https://doi.org/10.18502/ijph.v53i6.15914

Keywords: Sickle cell; Gene; Molecular pathway; Pathogenesis

Abstract

Background: Sickle cell disease (SCD) is one of the hematological disorders characterized by a defect in the structure and function of globin chains. Hereditary factors play an important role in the pathogenesis of SCD. We aimed to investigate the genes and pathways related to the pathogenesis of SCD.

Methods: Microarray dataset was downloaded from the Gene Expression Omnibus (GEO) database. LIMMA package of R-software was used to detect UP and Down regulations between SCD and control subjects. Enrichment analysis and Protein-protein interaction (PPI) networks were performed using GeneCodis4 software and GeneMANIA database, respectively. PrognoScan database was used to evaluate the relationship between the hub genes and patients' survival.

Results: Overall, 447 DEGs were identified in SCD patients compared to control subjects. Out of 447 DEGs, 345 genes were up-regulated and 102 genes were down-regulated. Effective hub genes in SCD pathogenesis include SLC4A1, DTL, EPB42, SNCA, and TOP2A. In addition, hub genes had a high diagnostic value.

Conclusion: Evaluation of hub genes in SCD can be used as a diagnostic panel to detect high-risk patients. In addition, by identifying the UP and Down stream pathways, treatment strategies in the monitoring and treatment of patients can be designed.