The Role of IL-6, TGF-β, and Genetic Variants in The ‎Pathophysiology of Thalassemia

  • Authors

    • Hamed Hussein Ali Al- Saadi Baghdad Directorate of Education, Rusafa III, Ministry of Education, Baghdad, Iraq
    • Muna Shukri Mahmood Al-Mashhadani Baghdad Directorate of Education, Rusafa II, Ministry of Education, Baghdad, Iraq
    • Haider Jassim Mohammed Baghdad Directorate of Education, Rusafa III, Ministry of Education, Baghdad, Iraq
    https://doi.org/10.14419/gx1v9h63

    Received date: June 25, 2025

    Accepted date: July 2, 2025

    Published date: October 12, 2025

  • Thalassemia; Inflammatory Cytokines; IL-6; TGF-Β; Genetic Factors

  • Abstract

    This study investigates the role of inflammatory cytokines and genetic ‎factors in thalassemia, a genetic blood disorder characterized by ‎chronic anemia and systemic complications. The study compared ‎levels of interleukin-6 (IL-6) and transforming growth factor-beta ‎‎(TGF-β) between thalassemia patients and healthy controls, as well as ‎analyzed genotype and allele frequencies to explore potential genetic ‎associations. Results showed significantly elevated levels of IL-6 ‎‎(25.88 ± 8.85 pg/ml vs. 14.32 ± 12.14 pg/ml, p < 0.001) and TGF-β ‎‎(1590.91 ± 413.31 pg/ml . 30.23 ± 16.19 pg/ml, p < 0.001) in ‎thalassemia patients, indicating a strong association with chronic ‎inflammation and fibrosis. Genetic analysis revealed that the AG ‎genotype and G allele were more frequent in controls (60% and 75%, ‎respectively) compared to patients (50% and 65%, p = 0.002 and p = ‎‎0.02), suggesting a potential protective effect. These findings highlight ‎the importance of cytokine dysregulation and genetic factors in the ‎pathophysiology of thalassemia. Elevated IL-6 and TGF-β levels may ‎serve as biomarkers for disease progression and complications, while ‎genetic profiling could aid in risk stratification and personalized ‎treatment strategies. Future research with larger cohorts is needed to ‎validate these findings and explore their clinical applications. This ‎study contributes to the growing understanding of thalassemia and ‎underscores the potential for targeted therapies to improve patient ‎outcomes‎.

  • References

    1. Bou-Fakhredin, R., Tabbikha, R., Daadaa, H., and Taher, A. T. (2020). Emerging therapies in β-thalassemia: toward a new era in management. Ex-pert opinion on emerging drugs, 25(2), 113–122. https://doi.org/10.1080/14728214.2020.1752180.
    2. Al-Barazanchi, A. Z. , Abdulateef, S.S. and Hassan, M. K. (2021). Co- Inheritance of α- thalassemia gene mutation in patients with sickle cell dis-ease: Impact on clinical and hematological variables. Nigerian journal of clinical practice, 24(6), 874-882. https://doi.org/10.4103/njcp.njcp_11_20.
    3. Gambari R. (2012). Alternative options for DNA-based experimental therapy of β-thalassemia. Expert opinion on biological therapy, 12(4), 443–462. https://doi.org/10.1517/14712598.2012.665047.
    4. Adnan I. Al-Badran, Meaad K. Hassan and Assad F. Washil. (2016). β-Thalassemia Mutations among Thalassemia Major Patients in Basrah Prov-ince – IraqInt.J.Curr.Microbiol.App.Sci. 5(5): 448-457. https://doi.org/10.20546/ijcmas.2016.505.047.
    5. Jahangiri, M., Rahim, F., Saki, N., & Saki Malehi, A. (2021). Application of Bayesian Decision Tree in Hematology Research: Differential Diagno-sis of β-Thalassemia Trait from Iron Deficiency Anemia. Computational and mathematical methods in medicine, 6401105. https://doi.org/10.1155/2021/6401105.
    6. Haj Khelil, A., Denden, S., Leban, N., Daimi, H., Lakhdhar, R., Lefranc, G., Ben Chibani, J., & Perrin, P. (2010). Hemoglobinopathies in North Africa: a review. Hemoglobin, 34(1), 1–23. https://doi.org/10.3109/03630260903571286.
    7. Goldman, L. and Schafer, A. I. (2010). Goldman-Cecil Medicine, Elsevier Health Sciences.
    8. Longo, F., Piolatto, A.; Ferrero, G.B.; Piga, A. (2021).Ineffective Erythropoiesis in beta-Thalassaemia: Key Steps and Therapeutic Options by Drugs. Int. J. Mol. Sci., 22, 7229. https://doi.org/10.3390/ijms22137229.
    9. Pietras, E.M.; Lakshminarasimhan, R.; Techner, J.M.; Fong, S.; Flach, J.; Binnewies, M.; Passegue, E. (2014). Re-entry into quiescence protects hematopoietic stem cells from the killing effect of chronic exposure to type I interferons. J. Exp. Med., 211, 245–262. https://doi.org/10.1084/jem.20131043.
    10. Cappellini, M. D., Cohen, A., Porter, J., Taher, A., & Viprakasit, V. (2020). Guidelines for the Management of Transfusion-Dependent Thalassaemia (TDT). Thalassaemia International Federation.
    11. Galarneau, G., Coady, S., & Garrett, M. E. (2010). Genetic modifiers of hemoglobinopathies. Current Opinion in Hematology, 17(3), 201-208.
    12. Gharagozloo, M., Karimi, M., & Amirghofran, Z. (2015). The role of inflammatory cytokines in the pathogenesis of thalassemia major. Cytokine, 73(2), 245-252.
    13. Makis, A., Hatzimichael, E., & Bourantas, K. L. (2017). The role of cytokines in the pathogenesis of thalassemia. Hematology, 22(5), 265-272.
    14. Musallam, K. M., Taher, A. T., Cappellini, M. D., & Sankaran, V. G. (2012). Clinical experience with fetal hemoglobin induction therapy in patients with β-thalassemia. Blood, 119(1), 219-226. https://doi.org/10.1182/blood-2011-09-382408.
    15. Taher, A. T., Weatherall, D. J., & Cappellini, M. D. (2018). Thalassaemia. The Lancet, 391(10116), 155-167. https://doi.org/10.1016/S0140-6736(17)31822-6.
    16. Vichinsky, E., Neufeld, E. J., & Cohen, A. (2018). Thalassemia: From bedside to genome and back. Hematology, 2018(1), 1-8.
    17. Vichinsky, E., Neufeld, E. J., & Cohen, A. (2018). Thalassemia: From bedside to genome and back. Hematology, 2018(1), 1-8.
    18. Thein, S. L. (2013). The molecular basis of β-thalassemia. Cold Spring Harbor Perspectives in Medicine, 3(5), a011700. https://doi.org/10.1101/cshperspect.a011700.
    19. Orter, J. B., & Garbowski, M. (2013). The pathophysiology of transfusional iron overload. Hematology/Oncology Clinics of North America, 27(4), 781-796. https://doi.org/10.1016/j.hoc.2014.04.003.
    20. Gharagozloo, M., Karimi, M., & Amirghofran, Z. (2015). The role of inflammatory cytokines in the pathogenesis of thalassemia major. Cytokine, 73(2), 245-252.

  • Downloads

  • How to Cite

    Al- Saadi , H. H. A. ., Al-Mashhadani , M. S. M., & Mohammed , H. J. . (2025). The Role of IL-6, TGF-β, and Genetic Variants in The ‎Pathophysiology of Thalassemia. International Journal of Basic and Applied Sciences, 14(6), 228-231. https://doi.org/10.14419/gx1v9h63