Effect of the Hemochromatosis Mutations on Iron Overload among the Indian β Thalassemia Carriers

Nadkarni, Anita; Singh, Aradhana A.; Colaco, Stacy; Hariharan, Priya; Colah, Roshan; Ghosh, Kanjaksha

doi:10.1002/jcla.22054

Cited by 8 publications

(3 citation statements)

References 22 publications

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“…[ 37 ] Some studies have indicated that the common mutation of the HFE gene (C282Y) causes a common type of hereditary hemochromatosis. [ 38 ] The H63D variant, a common polymorphism in the HFE gene, appears to modulate iron absorption. β-thalassemia carriers who are homozygous for the HFE H63D variant have higher serum ferritin levels than carriers without the variant.…”

Section: Resultsmentioning

confidence: 99%

“…Several genes implicated in iron homeostasis have been characterized, including those encoding homeostatic iron regulators (HFE), transferrin receptor 2, ferroportin, hepcidin, and hemojuvelin [37] . Some studies have indicated that the common mutation of the HFE gene (C282Y) causes a common type of hereditary hemochromatosis [38] . The H63D variant, a common polymorphism in the HFE gene, appears to modulate iron absorption.…”

Section: Resultsmentioning

confidence: 99%

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Molecular genetics of β-thalassemia

et al. 2021

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β-thalassemia is a hereditary hematological disease caused by over 350 mutations in the β-globin gene (HBB). Identifying the genetic variants affecting fetal hemoglobin (HbF) production combined with the α-globin genotype provides some prediction of disease severity for β-thalassemia. However, the generation of an additive composite genetic risk score predicts prognosis, and guide management requires a larger panel of genetic modifiers yet to be discovered.Presently, using data from prior clinical trials guides the design of further research and academic studies based on gene augmentation, while fundamental insights into globin switching and new technology developments have inspired the investigation of novel gene therapy approaches.Genetic studies have successfully characterized the causal variants and pathways involved in HbF regulation, providing novel therapeutic targets for HbF reactivation. In addition to these HBB mutation-independent strategies involving HbF synthesis de-repression, the expanding genome editing toolkit provides increased accuracy to HBB mutation-specific strategies encompassing adult hemoglobin restoration for personalized treatment of hemoglobinopathies. Allogeneic hematopoietic stem cell transplantation was, until very recently, the curative option available for patients with transfusion-dependent β-thalassemia. Gene therapy currently represents a novel therapeutic promise after many years of extensive preclinical research to optimize gene transfer protocols.We summarize the current state of developments in the molecular genetics of β-thalassemia over the last decade, including the mechanisms associated with ineffective erythropoiesis, which have also provided valid therapeutic targets, some of which have been shown as a proof-of-concept.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Molecular genetics of β-thalassemia

et al. 2021

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“…The role of H63D mutation polymorphism in β-thal major or carrier conditions has been studied in regions with a high incidence of H63D, such as in Southern Europe and Asia. Various studies have yielded conflicting conclusions (shown in Table 1): some studies from Italy, Portugal, India and Egypt suggested that iron overload might arise from the interacting effect of β-thal with homozygous or even heterozygous H 63 D mutations (13,(19)(20)(21)(22)(23); other reports from Italy, India, Thailand, Brazil and Spain indicated that the iron status was not related to the H63D mutation status (24)(25)(26)(27)(28)(29). The discrepancy may be due to the sample size, hereditary background variations in different racial populations, the sex ratio and the severity of thalassemia.…”

Section: Discussionmentioning

confidence: 99%

Late-onset Hemochromatosis: Co-inheritance of β-thalassemia and Hereditary Hemochromatosis in a Chinese Family: A Case Report and Epidemiological Analysis of Diverse Populations

et al. 2018

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Abstract:Hereditary hemochromatosis and β-thalassemia can both result in the inappropriately low production of the hormone hepcidin, which leads to an increase in intestinal absorption and excessive iron deposition in the parenchymal cells. To the best of our knowledge, there have been no reports on the coexistence of the two disorders in China. We herein report a case in a Chinese who presented with late-onset hepatic cirrhosis with hereditary hemochromatosis and β-thalassemia. We analyzed the pedigree of the two disorders and the iron status in his family members. Our case supports that a heterozygous H63D mutation can interact with β-thalassemia, leading to late-onset hemochromatosis.

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Impact of genotype on multi-organ iron and complications in patients with non-transfusion-dependent β-thalassemia intermedia

Meloni,

Pistoia,

Ricchi

et al. 2024

Ann Hematol

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Effect of the Hemochromatosis Mutations on Iron Overload among the Indian β Thalassemia Carriers

Abstract: This suggests that iron load in BTT tends to aggravated with the co-inheritance of the H63D mutation. The mutant H63D gene showed the presence of haplotype 6 which is reported in the European population suggesting a common origin.

Cited by 8 publications

References 22 publications

Molecular genetics of β-thalassemia

Molecular genetics of β-thalassemia

Late-onset Hemochromatosis: Co-inheritance of β-thalassemia and Hereditary Hemochromatosis in a Chinese Family: A Case Report and Epidemiological Analysis of Diverse Populations

Impact of genotype on multi-organ iron and complications in patients with non-transfusion-dependent β-thalassemia intermedia

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