Genetic Expression of FAS and miRNA34a-5P with β-Thalassemia Major in Iraqi Patients: A Case-Control Study
Keywords:
β-Thalassemia Major, FAS Gene Expression, miRNA-34a-5p, Gene Regulation, Hematological DisordersAbstract
Beta-thalassemia major (β-TM) is an inherited hematological disorder caused by mutations in the hemoglobin beta (HBB) gene, which encodes the β-globin chain; nevertheless, the micro ribonucleic acid 34a (miRNA34a-5P) gene is a key component of HBB gene defects. This miRNA34a-5P regulates fundamental aspects of erythroid cell survival, maturation and oxidative stress. Oxidative stress, excessive iron, and unpaired α-globin chains from decreased β-globin production may induce fetal alcohol syndrome (FAS) gene expression and thus increase the rate of apoptosis of erythroblasts. Thus, the gene expression of FAS and miRNA34a-5P was amplified and quantitatively by RT-qPCR in β-TM patients from Diwaniyah, Iraq and show relative to a housekeeping gene (GAPDH). When comparing the β-TM case (G2) with the control (G1), expression levels of both FAS and the microRNA34a were significantly different (). The second replication study confirms these above findings that the overexpression and amplification associated, respectively, of RT-PCR for FAS and miRNA34a-5P, as well that a correlation have been noted between the genes FAS and miR 34a with their appropriate diagnostic indication for the studied disease
Downloads
References
[1] D. C. Baird, S. H. Batten, and S. K. Sparks, “Alpha-and beta-thalassemia: rapid evidence reviews,” Am. Fam. Physician, vol. 105, no. 3, pp. 272–280. 2022.
[2] M. M. Salih, A. G. Al-Ziaydi, and A. H. H. Alzamili, “The Effect of Ferritin Level and Gene Expression of β-globin Promoter with β-thalassemia Patients in Al-Qadisiyah Governorate, Iraq,” J. Appl. Hematol, vol. 14, no. 4, pp. 257–262. 2023.
[3] S. Daar et al., “Mortality and complications in Omani patients with beta-thalassemia major: a long-term follow-up study,” Acta Bio Medica Atenei Parm, vol. 94, no. 4. 2023.
[4] S. M. Alharbi, S. S. Alshammari, H. A. Alsiaf, and F. S. Alkhowaiter, “Systematic review of metabolic and endocrinological complications in beta-thalassemia major: insights from 2021 to 2023,” Int. J. Med. Dev. Ctries, vol. 8, no. 1, p. 288.
[5] O. Raducka-Jaszul, D. M. Bogusławska, N. Jędruchniewicz, and A. F. Sikorski, “Role of extrinsic apoptotic signaling pathway during definitive erythropoiesis in normal patients and in patients with β-thalassemia,” Int. J. Mol. Sci, vol. 21, no. 9, p. 3325. 2020.
[6] E. Noulsri and S. Lerdwana, “Reducing erythroblast apoptosis in β-thalassemia via unfolded protein response (UPR) signaling,” Med. Hypotheses, vol. 177, p. 111117. 2022.
[7] K. Settakorn et al., “Effects of green tea extract treatment on erythropoiesis and iron parameters in iron-overloaded β-thalassemic mice,” Front. Physiol, vol. 13, p. 1053060. 2022.
[8] F. Wang, L. Ling, and D. Yu, “MicroRNAs in β-thalassemia,” Am. J. Med. Sci, vol. 362, no. 1, pp. 5–12. 2022.
[9] S. S. Das et al., “MicroRNA expression patterns in HbE/β-thalassemia patients: The passwords to unlock fetal hemoglobin expression in β-hemoglobinopathies,” Blood Cells, Mol. Dis, vol. 87, p. 102523. 2021.
[10] N. El-Khazragy et al., “Circulating miRNAs and tissue iron overload in transfusion-dependent β-thalassemia major: novel predictors and follow-up guide,” Ann. Hematol, vol. 100, no. 12, pp. 2909–2917. 2021.
[11] F. Shah et al., “Relationship between Serum Ferritin and Outcomes in β-Thalassemia: A Systematic Literature Review,” J. Clin. Med, vol. 11, no. 15, p. 4448. 2022.
[12] Y. S. Chang, L. Y. Hsiao, C. Y. Lin, M. C. Shih, M. C. Hsieh, and J. G. Chang, “Fasting glucose-to-HbA1c ratio is a good indicator of G6PD deficiency, but not thalassemia, in patients with type 2 diabetes mellitus,” Clin. Chim. Acta, vol. 506, pp. 9–15. 2023.
[13] K. S. Kumaravel, D. Sampathkumar, P. Punitha, V. Anurekha, M. Hema, and B. Rameshbabu, “Premature atherosclerosis in children with transfusion-dependent thalassemia: a twin-center cross-sectional study,” Indian Pediatr, vol. 59, no. 12, pp. 925–928. 2022.
[14] P. Ricchi et al., “Liver steatosis in patients with transfusion‐dependent thalassaemia,” Br. J. Haematol, vol. 204, no. 6, pp. 2458–2467. 2023.
[15] P. Mahakkanukrauh, A. Sinthubua, and S. Das, “Thalassemia Major and Bone Loss: Things to Ponder,” Int. Med. J, vol. 27, no. 2, pp. 185–187. 2022.
[16] G. S. Abdelmotaleb, O. G. Behairy, S. Hassan, and R. A. Khashaba, “Serum Levels of Ischemia Modified Albumin in Children with Β-Thalassemia Major,” Benha Med. J. 2023.
[17] A. Niaz, K. Tauseef, M. Zahid, H. Zafar, A. Nafisa, and N. Ikram, “Post Splenectomy Protein C Levels in Beta Thalassaemia Major Patients,” J. Haematol. Stem Cell Res, vol. 2, no. 2, pp. 85–89. 2021.
[18] A. Ahmadi et al., “Natural Anticoagulant Protein Levels in Patients With Beta-Thalassemia Major: A Case-Control Study,” J. Hematol, vol. 13, no. 1–2, p. 23. 2022.
[19] K. S. A. A. Neaimy, M. M. K. Alkhyatt, and I. A. Jarjess, “New Insights of Oxidative Stress and Thalassemia May Lead to Antioxidant Therapy,” Pharmacogn. J, vol. 16, no. 1. 2024.
[20] B. Akıncı, F. D. Yenigurbuz, A. Üstyol, and D. Ökdemir, “Thyroid Dysfunction in Beta-Thalassemia Major: Is It Related to Autoimmunity or Iron Overload?” Acıbadem Üniversitesi Sağlık Bilim. Derg, vol. 14, no. 3, pp. 377–382. 2023.
[21] A. Lal et al., “The transfusion management of beta thalassemia in the United States,” Transfusion (Paris)., vol. 61, no. 10, p. 3027. 2021.
[22] P. Z. Romadhon et al., “Markers of Renal Complications in Beta Thalassemia Patients with Iron Overload Receiving Chelation Agent Therapy: A Systematic Review,” J. Blood Med, pp. 725–738. 2023.
[23] Y. Sharif et al., “Assessment of patients with β-thalassemia major, undergoing tertiary care at a regional thalassemia center in Pakistan,” Pak. J. Zool, vol. 53, no. 1, p. 245. 2022.
[24] K. Trakarnsanga, N. Thongsin, C. Metheetrairut, C. Tipgomut, S. Poldee, and M. Wattanapanitch, “Genetic correction of haemoglobin E in an immortalised haemoglobin E/beta-thalassaemia cell line using the CRISPR/Cas9 system,” Sci. Rep, vol. 12, no. 1, p. 15551. 2022.
[25] M. Sanchez-Villalobos, M. Blanquer, J. M. Moraleda, E. J. Salido, and A. B. Perez-Oliva, “New insights into pathophysiology of β-thalassemia,” Front. Med, vol. 9, p. 880752. 2022.
[26] H. M. Sharshera, S. M. E. Maghraby, S. A. Aglan, I. L. Mikhael, and O. A. Balbaa, “Estimated Level of Plasma Micro RNA-210 in Beta Thalassemia Patients and Its Relation to Hemoglobin F Level and Disease Severity,” J. Appl. Hematol, vol. 14, no. 3, pp. 208–213. 2022.
[27] M. Rahaman et al., “Exploring the crosstalk between long non-coding RNAs and microRNAs to unravel potential prognostic and therapeutic biomarkers in β-thalassemia,” Mol. Biol. Rep, vol. 49, no. 7, pp. 7057–7068. 2022
[28] L. Conceição Braga, B. Ô. P. Gonçalves, P. L. Coelho, A. L. Silva Filho, and L. M. Silva, “Identification of best housekeeping genes for the normalization of RT-qPCR in human cell lines,” Acta Histochem, vol. 124, no. 1, p. 151821. 2022.
[29] Y. Li, Q. Ma, X. Shi, W. Yuan, G. Liu, and C. Wang, “Comparative transcriptome analysis of slow-twitch and fast-twitch muscles in dezhou donkeys,” Genes (Basel, vol. 13, no. 9. 2022.
[30] L. Wang, Y. Xie, W. Chen, Y. Zhang, and Y. Zeng, “miR-34a regulates lipid droplet deposition in 3T3-L1 and C2C12 cells by targeting LEF1,” Cells, vol. 12, no. 1, p. 167. 2023.
[31] Y. P. Chen, C. C. Hu, S. Tsai, Z. H. Wen, and C. Lin, “Identification of housekeeping gene for future studies exploring effects of cryopreservation on gene expression in shrimp,” Sci. Rep, vol. 15, no. 1, p. 11046. 2023.
[32] A. Formosa et al., “Validation of reference gene stability for miRNA quantification by reverse transcription quantitative PCR in the peripheral blood of patients with COVID-19 critical illness,” PLoS One, vol. 18, no. 8, p. 286871. 2023.
[33] Y. Wang, F. Zhou, M. Li, Y. Zhang, N. Li, and L. Shao, “MiR-34a-5p promotes hepatic gluconeogenesis by suppressing SIRT1 expression,” Exp. Cell Res, vol. 420, no. 1, p. 113336. 2022.
[34] H. T. Ong, C. M. Prêle, and R. J. Dilley, “Using RNA-seq to identify suitable housekeeping genes for hypoxia studies in human adipose-derived stem cells,” BMC Mol. cell Biol, vol. 24, no. 1, p. 16. 2023.
[35] A. D. Singh et al., “Identifying stable reference genes in polyethene glycol precipitated urinary extracellular vesicles for RT-qPCR-based gene expression studies in renal graft dysfunction patients,” Transpl. Immunol, vol. 75, p. 101715. 2023.
[36] R. R. Su, Z. Y. Huang, C. W. Qin, X. L. Zheng, W. Lu, and X. Y. Wang, “Evaluation of reference genes in Glenea cantor (Fabricius) by using qRT-PCR,” Genes (Basel, vol. 12, no. 12. 2021.
Downloads
Published
Issue
Section
Categories
License
Copyright (c) 2026 Al-Zahrawi Journal of Medical Sciences

This work is licensed under a Creative Commons Attribution 4.0 International License.







