Tehran University of Medical Sciences Iranian Journal of Public Health 2251-6085 53 6 2024 06 11 1404 1415 Reza Maddah Department of Bioprocess Engineering, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering 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, Tehran, 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 Transfusion Organization (IBTO), Tehran, Iran 2023 03 09 2023 08 22 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. https://ijph.tums.ac.ir/index.php/ijph/article/view/31431 https://ijph.tums.ac.ir/index.php/ijph/article/download/31431/8273