Exploring Transferrin Gene Expression as A Biomarker of Ineffective Erythropoiesis and Iron Overload in HbE/β-Thalassemia and β-Thalassemia Trait

Abstract

INTRODUCTION: Iron overload is a major concern in transfusion-dependent thalassaemia patients, with soluble transferrin receptors (sTfR) playing a key role in iron regulation. This study aimed to evaluate the gene expression of TfR1 and TfR2 and their association with ineffective erythropoiesis (IE) and iron overload in HbE/β-thalassaemia patients. MATERIALS AND METHODS: A total of 2 ml whole peripheral blood was extracted for RNA from 6 subjects recruited from each HbE/β-thalassaemia patient, β-thalassaemia trait carriers, and healthy controls. TfR levels were measured using ELISA, while TfR1 and TfR2 gene expression were assessed using RT-qPCR. Data were analysed using ANOVA, Student’s t-test, Kruskal–Wallis, and Mann–Whitney U tests with Bonferroni correction. RESULTS: Gene expression analysis revealed a significant downregulation of TfR2 in HbE/β-thalassaemia patients and β-thalassaemia carriers (P<0.001) compared to healthy controls, while TfR1 expression was significantly upregulated (P<0.001). Additionally, sTfR levels were statistically higher in HbE/β-thalassaemia patients and parents compared to healthy controls (P<0.001). CONCLUSION: These findings suggest that TfR1 and TfR2 expression patterns may serve as potential biomarkers for assessing IE and iron overload in β-thalassaemia. Furthermore, elevated sTfR levels indicated that the transfusion regimen was insufficient to suppress ineffective erythropoiesis. In β-thalassaemia intermedia patients, haemoglobin levels may not be the most reliable marker for monitoring transfusion therapy, whereas sTfR could help in tailoring individualised transfusion regimens.