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

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

Iran J Public Health. 2024 Jun;53(6):1404-1415.

Authors

Reza Maddah¹, Sareh Etemad², Bahareh Shateri Amiri³, Hajarossadat Ghaderi⁴, Hamidreza Zarei⁵, Ferdos Faghihkhorasani⁶, Hadi Rezaeeyan⁷

Affiliations

¹ Department of Bioprocess Engineering, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
² Department of Pathology, Faculty of Anatomical Pathology Ghaem Hospital, University of Medicine, Mashhad, Iran.
³ Department of Internal Medicine, School of Medicine Hazrat-e Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran.
⁴ Laboratory of Regenerative and Medical Innovation, Pasteur Institute of Iran, Tehran, Iran.
⁵ Department of Internal Medicine, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
⁶ Medical Campus, Xian Jiaotong University, Xian, Shaanxi Province, China.
⁷ Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Iranian Blood Transfusion Organization (IBTO), Tehran, Iran.

PMID: 39430157
PMCID: PMC11488559

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.

Keywords: Gene; Molecular pathway; Pathogenesis; Sickle cell.