Saad Hanan Kamel M, Taib Wan Rohani Wan, Ismail Imilia, Johan Muhammad Farid, Al-Wajeeh Abdullah Saleh, Al-Jamal Hamid Ali Nagi
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.
Exp Ther Med. 2021 Dec;22(6):1402. doi: 10.3892/etm.2021.10838. Epub 2021 Oct 4.
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.
铁稳态由铁调素（HEPC）调节，铁调素控制膳食铁吸收和铁循环。铁调素缺乏会导致β地中海贫血患者出现铁过载。本研究旨在调查血红蛋白E（HbE）/β地中海贫血患者及其父母（HbE特征和β地中海贫血特征）与健康对照者相比，铁调素浓度与血清铁状态之间的相关性。本研究是一项比较性横断面研究，在马来西亚丁加奴州苏丹娜努尔·扎希拉医院对65例HbE/β地中海贫血患者（输血前）和65名父母进行了铁代谢指标和铁调素水平检测，并在苏丹再纳阿比丁大学选取130名学生作为健康对照。此外，从每组（HbE/β地中海贫血患者、父母和健康对照）中随机抽取6个样本，使用逆转录定量PCR对铁调素和铁转运蛋白1（FPN1）进行基因表达分析。结果表明，与健康对照相比，HbE/β地中海贫血患者及其父母的血清铁调素水平显著降低（P<0.001）。此外，基因表达分析显示，与健康对照相比，HbE/β地中海贫血患者及其父母的铁调素基因表达显著下调（P=0.001）。然而与健康对照相比，HbE/β地中海贫血患者及其父母的FPN1显著上调（P=0.001）。铁代谢指标结果显示，与健康对照相比，HbE/β地中海贫血患者及其父母的血清铁蛋白显著升高（P<0.001）。总之，本研究表明，HbE/β地中海贫血患者及其父母的铁调素表达水平和血清水平显著降低，与健康志愿者相比，FPN1表达水平和血清铁蛋白水平显著升高。这些发现支持了以下假设：铁调素下调会使其作为FPN1负调节因子的功能丧失，导致HbE/β地中海贫血患者出现铁过载。随后，评估铁调素和FPN1基因表达可能是确定HbE/β地中海贫血患者及其父母铁毒性风险的有用工具，因此可被视为这些患者铁负荷管理的治疗靶点。
