Two missense mutations (p.H63D and p.C282Y) in HFE gene elevate the risk of iron-overload in HbE/β-thalassemia disease

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-02-11 DOI:10.1016/j.genrep.2025.102165

Motiur Rahaman , Shatarupa Bhattacharya , Ramya Vaddi , Mandrita Mukherjee , Doyel Mani , Manisha Jain , Tuphan Kanti Dolai , Prantar Chakrabarti , Shashank Purwar , Bhavna Dhingra , Praphulla Chandra Shukla , Gayatri Mukherjee , Budhaditya Mukherjee , Nishant Chakravorty

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引用次数: 0

Abstract

Iron-overload is reported to be one of the major complications associated with HbE/β-thalassemia. Studies show that iron overload is often associated with both, transfusion-dependent thalassemia (TDT) and non-transfusion dependent thalassemia (NTDT) patients. Our results demonstrate that iron overloading, which is a known complication in HbE/β-thalassemia, is further aggravated with the coinheritance of HFE mutations (H63D and C282Y) even in heterozygous state. In the present study, we provide evidence that HFE mutations, p.H63D and p.C282Y, are associated with iron-overload condition and may act as genetic predisposition factors, in elevating the risk of iron overload in Indian HbE/β-thalassemia patients. Furthermore, we also identified significant association between human leukocyte antigen (HLA) alleles such as HLA-C*07, DRB1*15, DQB1*05, etc. with HFE gene mutations. These data suggest the importance of epidemiological studies on complex genetic mutations in HbE/β-thalassemia patients, and are a valuable contribution to a perspective study on iron-overload in HbE/β-thalassemia disease. Additional studies should consider larger patient cohort to further validate these effects of HFE mutations on iron overload in HbE/β-thalassemia disease.

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HFE基因的两个错义突变（p.H63D和p.C282Y）增加了HbE/β-地中海贫血病中铁超载的风险

据报道，铁超载是HbE/β-地中海贫血的主要并发症之一。研究表明，铁超载通常与输血依赖型地中海贫血（TDT）和非输血依赖型地中海贫血（NTDT）患者相关。我们的研究结果表明，即使在杂合状态下，HFE突变（H63D和C282Y）的共遗传也会进一步加剧铁超载，这是HbE/β-地中海贫血的已知并发症。在本研究中，我们提供的证据表明，HFE突变p.H63D和p.C282Y与铁超载状况有关，并可能作为遗传易感性因素，在印度HbE/β-地中海贫血患者中增加铁超载的风险。此外，我们还发现HLA- c *07、DRB1*15、DQB1*05等人类白细胞抗原（HLA）等位基因与HFE基因突变之间存在显著相关性。这些数据提示了HbE/β-地中海贫血患者复杂基因突变流行病学研究的重要性，并为HbE/β-地中海贫血疾病铁超载的前瞻性研究做出了有价值的贡献。进一步的研究应考虑更大的患者队列，以进一步验证HFE突变对HbE/β-地中海贫血疾病中铁超载的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.