Texila International Journal of Public Health ISSN: 2520-3134 DOI: 10.21522/TIJPH.2013.13.01.Art067 Received: 25.11.2024 Accepted: 04.02.2025 Published on: 28.03.2025 *Corresponding Author: alnorimkj@uomosul.edu.iq The Harmony of Iron Regulating Genes and Genes of Antioxidant Enzymes in Thalassaemia Patients Nuha S. Thanoon 1 , Mohammed K. J. Alnori 2* , Ali S. Alchalabi 3 1 Ninevah Health, Ninevah, Iraq 2 College of Pharmacy, University of Mosul, Mosul, Iraq 3 College of Veterinary Medicine, University of Mosul, Mosul, Iraq Abstract The purpose of this work was to investigate the expression of iron-regulating genes and their relationship to enzymatic antioxidant genes in thalassaemic patients, as well as to detect distinct forms of thalassaemia using an RT-PCR technique using a presence/absence protocol. This study included 50 patients who were admitted to Mosul's Al-Hadba'a Hospital. Ten healthy subjects and forty thalassaemic patients were aged eight to seventeen years. Freshly blood samples were collected using EDTA for molecular processes, as gene expression and genomic identification of thalassaemia types. The outcomes indicated that the foxO1 gene was significantly upregulated in thalassaemic patients compared to healthy participants, but hepcidin expression was non-significantly downregulated. Similarly, the enzymatic antioxidant gene GSH-Px1 demonstrated significant downstream regulation expression in thalassaemic participants compared to healthy ones, even though the expression of SOD1 and CAT antioxidant enzyme genes did not differ across investigated patients. Catalase expression is associated inversely with foxO1 expression. The presence/absence approach showed that 8.4% and 5.1% of individuals had positive α-thalassaemia based on α1 and α2 mutations in their gDNA samples, respectively, compared to healthy patients. Furthermore, 33.6%, 36.5%, and 16.4% of blood samples with an unknown type of thalassaemia tested positive for ß- thalassaemia because their gDNA samples had codon8/9, codon 41/42, and IVS-I-5 mutations, respectively. Our findings suggest that the RT-PCR approach is the most effective for studying gene expression and molecular identification of thalassaemia types. Keywords: Antioxidant Enzymes, Foxo1, Hepcidin, Thalassemia. Introduction Many biological functions require iron, a mineral that can be hazardous in excess. The body has to control how much iron it gets from food since it cannot expel excess iron [1]. Hepcidin is a hormone produced in the liver that mediates this control [2]. Additionally, hepcidin regulates the release of iron from hepatocytes, which store iron, and macrophages, which recycle iron. Hepcidin inhibits the release of iron into the plasma by binding to ferroportin, the sole known iron export protein, and causing its internalization and destruction [3]. The following factors significantly influence hepcidin and, by extension, systemic iron homeostasis: body iron storage, infection and inflammation, hypoxia and erythropoiesis, and, to a lesser extent, testosterone [4]. Overproduction of hepcidin leads to iron- restricted anaemias in chronic inflammatory diseases and inherited iron-refractory anaemia, while deficiency causes iron overload in hereditary hemochromatosis and non- transfused β-thalassemia [5]. Strong radicals can be created from relatively stable oxidants