Hereditary hemochromatosis: The complex role of the modifier genes

Biasiotto, Giorgio; Carini, Mattia; Bresciani, Roberto; Ferrari, Fabiana

doi:10.1016/j.jtemb.2023.127248

Cited by 2 publications

(2 citation statements)

References 6 publications

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“…The SLE + RA cohort was statistically significant when compared with all of the control populations employed. Curiously, the p.Cys282Tyr mutation is the main mutation responsible for hereditary hemochromatosis (HH) and is characterized by incomplete penetrance [5,39]. Not much has been reported in the literature about this mutation and autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

Frequency Evaluation of the Interleukin-6 −174G>C Polymorphism and Homeostatic Iron Regulator (HFE) Mutations as Disease Modifiers in Patients Affected by Systemic Lupus Erythematosus and Rheumatoid Arthritis

Carini,

Fredi,

Cavazzana

et al. 2023

IJMS

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Autoimmune diseases are generally characterized by a multifactorial etiology and are often associated with a genetic predisposition. Both iron metabolism and the inflammatory cytokine system have been shown to play a pivotal role in the dysregulation of the immune response in many different autoimmune conditions, rheumatologic diseases included. The purpose of this work was to analyze the frequency of mutations altering the expression of IL-6 or influencing iron metabolism in patients affected by autoimmune diseases such as Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE). In this study, 144 patients were enrolled: 77 and 67 patients were affected by RA and SLE, respectively. In these cohorts, the frequency of the IL-6 polymorphism −174G>C located in the IL-6 gene promoter was tested. Moreover, the frequencies of the three HFE gene variations associated with iron overload were analyzed: p.His63Asp, p.Ser65Cys and p.Cys282Tyr. The two mutations p.His63Asp and p.Ser65Cys in the HFE gene did not reach statistical significance in any of the comparisons, regardless of the statistical model, cohorts of patients and control populations analyzed. The frequencies of the p.Cys282Tyr mutation and the IL-6 polymorphism −174G>C were found to be overall significantly decreased in RA and SLE patients when the Dominant model and Allele contrast were adopted with both the Odds Ratio and Chi-square. Although further investigation is needed, the examination of the frequencies of the −174G>C IL-6 promoter polymorphism and HFE mutations may add some valuable information on the interplay linking iron metabolism, inflammation and immunity in autoimmune diseases such as SLE and RA.

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Section: Discussionmentioning

confidence: 99%

Frequency Evaluation of the Interleukin-6 −174G>C Polymorphism and Homeostatic Iron Regulator (HFE) Mutations as Disease Modifiers in Patients Affected by Systemic Lupus Erythematosus and Rheumatoid Arthritis

Carini,

Fredi,

Cavazzana

et al. 2023

IJMS

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“…On the contrary, when the body needs iron such as in iron deficiency, anemia, hypoxia or when it is necessary to increase erythropoietic activity, the synthesis of hepcidin is inhibited, allowing iron absorption from the enterocytes and iron release from the spleen macrophages and from the stores [11,12]. Mutations in genes codifying for proteins involved in the process of iron sensing can cause an iron overload pathology known as Hereditary Hemochromatosis [13][14][15]. Iron metabolism is also conditioned by inflammation, and Interleukin 6 (IL-6) has been described to be an important inducer of hepcidin synthesis via the JAK/STAT3 inflammatory pathway [16,17].…”

Section: Introductionmentioning

confidence: 99%

Potential Diagnostic Role of Hepcidin in Anemic Patients Affected by Inflammatory Bowel Disease: A Systematic Review

Ferrari,

Carini,

Zanella

et al. 2024

Diagnostics

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Background: Anemia is the main extraintestinal comorbidity of Inflammatory Bowel Disease (IBD). Differentiating the type of anemia in these disorders is still a challenge. Hepcidin could be a promising biomarker to identify iron deficiency anemia (IDA), anemia of chronic disease (ACD) and the concomitant presence of both IDA and ACD. Methods: To evaluate the potential role of hepcidin dosage in the management of anemia in IBD patients, we performed a systematic review by a comprehensive literature analysis of original papers reporting the dosage of hepcidin in IBD patients. In all the articles reviewed, the dosage of ferritin was reported, and the correlation between hepcidin and ferritin has been used to compare these two biomarkers. Results: A total of 12 articles concerning the dosage of hepcidin in IBD were included, comprising in total of 976 patients. The results of the hepcidin values in IBD patients when compared with controls were conflicting. In fact, four articles described an increase in this biomarker, three showed a decrease and five did not find significant differences. The correlation with ferritin was positive and significant. In three studies, some differences between hepcidin dosages and ferritin levels indicate a possible role when IDA and ACD could be present at the same time. Conclusions: Considering the contradictory data of the studies, the diagnostic role of hepcidin as a biomarker remains elusive in IBD patients. These differences could be due to the clinical characteristics of the patients enrolled that should be better defined in the future. A suitable clinical trial should be designed to outline the possible role of hepcidin in differentiating IDA, ACD and concomitant IDA and ACD in IBD patients. At the moment, ferritin still remains the best marker to diagnose these conditions, in addition to hemoglobin, transferrin saturation and CRP as recommended by the ECCO guidelines.

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Hereditary hemochromatosis: The complex role of the modifier genes

Cited by 2 publications

References 6 publications

Frequency Evaluation of the Interleukin-6 −174G>C Polymorphism and Homeostatic Iron Regulator (HFE) Mutations as Disease Modifiers in Patients Affected by Systemic Lupus Erythematosus and Rheumatoid Arthritis

Frequency Evaluation of the Interleukin-6 −174G>C Polymorphism and Homeostatic Iron Regulator (HFE) Mutations as Disease Modifiers in Patients Affected by Systemic Lupus Erythematosus and Rheumatoid Arthritis

Potential Diagnostic Role of Hepcidin in Anemic Patients Affected by Inflammatory Bowel Disease: A Systematic Review

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