Reduced hepcidin expression enhances iron overload in patients with HbE/β‑thalassemia: Α comparative cross‑sectional study

Saad,Hanan Kamel M.; Taib,Wan Rohani Wan; Ismail,Imilia; Johan,Muhammad Farid; Al‑Wajeeh,Abdullah Saleh; Al‑Jamal,Hamid Ali Nagi

doi:10.3892/etm.2021.10838

Reduced hepcidin expression enhances iron overload in patients with HbE/β‑thalassemia: Α comparative cross‑sectional study

Authors:
- Hanan Kamel M. Saad
- Wan Rohani Wan Taib
- Imilia Ismail
- Muhammad Farid Johan
- Abdullah Saleh Al‑Wajeeh
- Hamid Ali Nagi Al‑Jamal
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Affiliations: School of Biomedicine, Faculty of Health Sciences, Universiti Sultan Zainal Abidin, Gong Badak Campus, 21300 Terengganu, Kelantan, Malaysia, Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, 16150 Kota Bharu, Kelantan, Malaysia, Anti‑Doping Lab Qatar, Doha, Qatar
Published online on: October 4, 2021 https://doi.org/10.3892/etm.2021.10838
Article Number: 1402
Copyright: © Saad et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Iron homeostasis is regulated by hepcidin (HEPC) that controls the dietary iron absorption and iron recycling. HEPC deficiency contributes to iron overload in β‑thalassemia patients. The present study aimed to investigate the correlation between HEPC concentration and serum iron status among hemoglobin E (HbE)/β‑thalassemia patients and their parents (HbE trait and β‑thalassemia trait) compared with healthy controls. This study is a comparative cross‑sectional study in which iron profile and HEPC level were examined in 65 HbE/β‑thalassemia patients (pretransfusion) and 65 parents at the Hospital Sultanah Nur Zahirah and in 130 students as healthy controls from Univesiti Sultan Zainal Abidin, Terengganu, Malaysia. Furthermore, six samples from each group (HbE/β‑thalassemia patients, parents and healthy controls) were randomly selected for gene expression analysis of HEPC and ferroportin1 (FPN1) using reverse transcription quantitative PCR. The results demonstrated that serum HEPC level were significantly decreased in HbE/β‑thalassemia patients and their parents (P<0.001) compared with healthy controls. In addition, the gene expression analysis showed a dramatically downregulated HEPC in HbE/β‑thalassemia patients and their parents (P=0.001) compared with healthy controls. However, there was a marked upregulation of FPN1 in HbE/β‑thalassemia patients and their parents (P=0.001) compared with healthy controls. Iron profiling results revealed a significantly increased serum ferritin in HbE/β‑thalassemia patients and their parents compared with healthy controls (P<0.001). In summary, the present study demonstrated that HEPC expression level and serum level were significantly decreased in HbE/β‑thalassemia patients and their parents, which was combined with a marked increased FPN1 expression level and serum ferritin level compared with healthy volunteers. These findings supported the hypothesis that downregulated HEPC could lose its function as a negative regulator of FPN1, resulting in iron overload in HbE/β‑thalassemia patients. Subsequently, assessing HEPC and FPN1 gene expression may be a useful tool to determine the risk of iron toxicity in patients with HbE/β‑thalassemia and their parents, and could therefore be considered as a therapeutic target in the management of iron burden in these patients.

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