Expression of the FAM132B Gene in Iranian Patients with Beta-Thalassemia
Abstract
Background: Iron homeostasis is a complex process involving multiple factors. Erythroblasts secrete erythroferrone (ERFE), which affects hepcidin production, thereby enhancing iron uptake. This study aimed to investigate the expression of the ERFE-encoding FAM132B gene in Iranian patients with beta-thalassemia major (BTM) and beta-thalassemia intermedia (BTI).
Materials and Methods: A total of 40 BTM and BTI patients and 20 healthy blood donors as a control group were recruited. Total RNA was extracted from whole blood samples, and cDNA was synthesized. Gene expression was quantified using a SYBR Green-based real-time PCR (RT-PCR) assay. Data analysis was performed by the GraphPad Prism program using the one-way ANOVA test.
Results: The expression of the FAM132B gene was upregulated in BTI patients compared to BTM patients (p = 0.0151). Despite the higher mRNA fold change in BTI patients, no significant difference was observed in the FAM132B gene expression between beta-thalassemia patients (major and intermedia) and the control group.
Conclusion: The expression of the FAM132B gene was different between beta-thalassemia major and intermedia patients. Further studies should be conducted to better elucidate the role of erythroferrone as a potential therapeutic target in patients with beta-thalassemia.
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17. El Gendy FM, EL‐Hawy MA, Shehata AMF, et al. Erythroferrone and iron status parameters levels in pediatric patients with iron deficiency anemia. Eur J Haematol. 2018;100(4): 356-60.
18. Latour C, Wlodarczyk MF, Jung G, et al. Erythroferrone contributes to hepcidin repression in a mouse model of malaria anemia. Haematologica. 2017;102(1): 60-8.
19. Kautz L, Jung G, Du X, et al. Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of β-thalassemia. Blood. 2015;126(17): 2031-7.
20. Nemeth E, Ganz T. The role of hepcidin in iron metabolism. Acta Haematol. 2009;122(2-3): 78-86.
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23. El-Gamal RAE, Abdel-Messih IY, Habashy DM, et al. Erythroferrone, the new iron regulator: Evaluation of its levels in Egyptian patients with beta-thalassemia. Ann Hematol. 2020;99(1): 31-9.
24. Cappellini MD, Cohen A, Eleftheriou A, et al. Guidelines for the Clinical Management of Thalassaemia [Internet]. 2nd edition. Nicosia (CY): Thalassaemia International Federation; 2008.
25. Dore F, Bonfigli S, Gaviano E, et al. Serum erythropoietin levels in thalassemia intermedia. Ann Hematol. 1993;67(4): 183-6.
26. Ganz T, Jung G, Naeim A, et al. Immunoassay for human serum erythroferrone. Blood. 2017;130(10): 1243-6.
27. Pasricha SR, Frazer DM, Bowden DK, et al. Transfusion suppresses erythropoiesis and increases hepcidin in adult patients with β-thalassemia major: a longitudinal study. Blood. 2013;122(1): 124-33.
28. Iolascon A, Heimpel H, Wahlin A, et al. Congenital dyserythropoietic anemias: molecular insights and diagnostic approach. Blood. 2013;122(13): 2162-6.
29. Russo R, Andolfo I, Manna F, et al. Increased levels of ERFE-encoding FAM132B in patients with congenital dyserythropoietic anemia type II. Blood. 2016;128(14): 1899-902.
30. Ribeil JA, Arlet JB, Dussiot M, et al. Ineffective erythropoiesis in β-thalassemia. ScientificWorldJournal. 2013;2013: 394295.
31. Olivera J, Zhang V, Nemeth E, et al. Erythroferrone exacerbates iron overload and ineffective extramedullary erythropoiesis in a mouse model of β-thalassemia. Blood Adv. 2023;7(14): 3339-49.
32. Zarghamian P, Azarkeivan A, Arabkhazaeli A, et al. Hepcidin gene polymorphisms and iron overload in β-thalassemia major patients refractory to iron chelating therapy. BMC Med Genet. 2020;21(1): 75.
33. Parajes S, González-Quintela A, Campos J, et al. Genetic study of the hepcidin gene (HAMP) promoter and functional analysis of the c.-582A > G variant. BMC Genet. 2010;11: 110.
2. Cao A, Galanello R. Beta-thalassemia. Genet Med. 2010;12(2): 61-76.
3. Marvasti VE, Dastoori P, Karimi M. Is beta-thalassemia trait a risk factor for developing depression in young adults?. Ann Hematol. 2006;85(12): 873-4.
4. Hadipour Dehshal M, Tabrizi Namini M, Hantoushzadeh R, et al. β-Thalassemia in Iran: Things Everyone Needs to Know About This Disease. Hemoglobin. 2019;43(3): 166-73.
5. Miri M, Tabrizi Namini M, Hadipour Dehshal M, et al. Thalassemia in Iran in the Last Twenty Years: the Carrier Rates and the Birth Trend. Iran J Blood Cancer. 2013;6(1): 11-7.
6. Origa R. β-Thalassemia. Genet Med. 2017;19(6): 609-19.
7. Patterson S, Singleton A, Branscomb J, et al. Transfusion Complications in Thalassemia: Patient Knowledge and Perspectives. Front Med (Lausanne). 2022;9:772886.
8. Makis A, Hatzimichael E, Papassotiriou I, et al. 2017 Clinical trials update in new treatments of β‐thalassemia. Am J Hematol. 2016;91(11): 1135-45.
9. Casu C, Rivella S. Iron age: novel targets for iron overload. Hematology Am Soc Hematol Educ Program. 2014;2014(1): 216-21.
10. Yiannikourides A, Latunde-Dada GO. A short review of iron metabolism and pathophysiology of iron disorders. Medicines (Basel). 2019;6(3): 85.
11. Kautz L, Jung G, Nemeth E, et al. Erythroferrone contributes to recovery from anemia of inflammation. Blood. 2014;124(16): 2569-74.
12. Than MM, Koonyosying P, Ruangsuriya J, et al. Effect of Recombinant Human Erythroferrone Protein on Hepcidin Gene (Hamp1) Expression in HepG2 and HuH7 Cells. Materials (Basel). 2021;14(21): 6480.
13. Kautz L, Jung G, Valore EV, et al. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet. 2014;46(7): 678-84.
14. Babar S, Saboor M. Erythroferrone in focus: emerging perspectives in iron metabolism and hematopathologies. Blood Sci. 2024;6(4): e00198.
15. Hanudel MR, Rappaport M, Chua K, et al. Levels of the erythropoietin-responsive hormone erythroferrone in mice and humans with chronic kidney disease. Haematologica. 2018;103(4): e141-2.
16. Saad HE, Bahgat SM, El Dewy DM, et al. Erythroferrone level in β-thalassemia patients. JRAM. 2021;2(1):1-9.
17. El Gendy FM, EL‐Hawy MA, Shehata AMF, et al. Erythroferrone and iron status parameters levels in pediatric patients with iron deficiency anemia. Eur J Haematol. 2018;100(4): 356-60.
18. Latour C, Wlodarczyk MF, Jung G, et al. Erythroferrone contributes to hepcidin repression in a mouse model of malaria anemia. Haematologica. 2017;102(1): 60-8.
19. Kautz L, Jung G, Du X, et al. Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of β-thalassemia. Blood. 2015;126(17): 2031-7.
20. Nemeth E, Ganz T. The role of hepcidin in iron metabolism. Acta Haematol. 2009;122(2-3): 78-86.
21. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306(5704):2090-3.
22. Liu J, Sun B, Yin H, et al. Hepcidin: A Promising Therapeutic Target for Iron Disorders: A Systematic Review. Medicine (Baltimore). 2016;95(14): e3150.
23. El-Gamal RAE, Abdel-Messih IY, Habashy DM, et al. Erythroferrone, the new iron regulator: Evaluation of its levels in Egyptian patients with beta-thalassemia. Ann Hematol. 2020;99(1): 31-9.
24. Cappellini MD, Cohen A, Eleftheriou A, et al. Guidelines for the Clinical Management of Thalassaemia [Internet]. 2nd edition. Nicosia (CY): Thalassaemia International Federation; 2008.
25. Dore F, Bonfigli S, Gaviano E, et al. Serum erythropoietin levels in thalassemia intermedia. Ann Hematol. 1993;67(4): 183-6.
26. Ganz T, Jung G, Naeim A, et al. Immunoassay for human serum erythroferrone. Blood. 2017;130(10): 1243-6.
27. Pasricha SR, Frazer DM, Bowden DK, et al. Transfusion suppresses erythropoiesis and increases hepcidin in adult patients with β-thalassemia major: a longitudinal study. Blood. 2013;122(1): 124-33.
28. Iolascon A, Heimpel H, Wahlin A, et al. Congenital dyserythropoietic anemias: molecular insights and diagnostic approach. Blood. 2013;122(13): 2162-6.
29. Russo R, Andolfo I, Manna F, et al. Increased levels of ERFE-encoding FAM132B in patients with congenital dyserythropoietic anemia type II. Blood. 2016;128(14): 1899-902.
30. Ribeil JA, Arlet JB, Dussiot M, et al. Ineffective erythropoiesis in β-thalassemia. ScientificWorldJournal. 2013;2013: 394295.
31. Olivera J, Zhang V, Nemeth E, et al. Erythroferrone exacerbates iron overload and ineffective extramedullary erythropoiesis in a mouse model of β-thalassemia. Blood Adv. 2023;7(14): 3339-49.
32. Zarghamian P, Azarkeivan A, Arabkhazaeli A, et al. Hepcidin gene polymorphisms and iron overload in β-thalassemia major patients refractory to iron chelating therapy. BMC Med Genet. 2020;21(1): 75.
33. Parajes S, González-Quintela A, Campos J, et al. Genetic study of the hepcidin gene (HAMP) promoter and functional analysis of the c.-582A > G variant. BMC Genet. 2010;11: 110.
| Files | ||
| Issue | Vol 19 No 4 (2025) | |
| Section | Original Article(s) | |
| Keywords | ||
| Beta-thalassemia; Gene expression; Erythroferrone (ERFE); FAM132B; Iron overload | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Sarem F, Azarkeivan A, Mardani A, Shahabi M. Expression of the FAM132B Gene in Iranian Patients with Beta-Thalassemia. Int J Hematol Oncol Stem Cell Res. 2025;19(4):338-343.
