Association of HFE and TMPRSS6 genetic variants with iron and erythrocyte parameters is only in part dependent on serum hepcidin concentrations
Abstract
Background: Hepcidin is the main regulator of iron homeostasis: inappropriate production of hepcidin results in iron overload or iron deficiency and anaemia. Aims: To study variation of serum hepcidin concentration in a normal population. Results: Hepcidin showed age and sex dependent variations that correlated with ferritin but not with serum iron and transferrin saturation. The size of the study population was underpowered to find genome wide significant associations with hepcidin concentrations but it allowed to show that association with serum iron, transferrin saturation and erythrocyte traits of common DNA variants in HFE (rs1800562) and TMPRSS6 (rs855791) genes is not exclusively dependent on hepcidin values. When multiple interactions between environmental factors, the iron parameters and hepcidin were taken into account, the HFE variant, and to lesser extent the TMPRSS6 variant, were associated with ferritin and with hepcidin normalised to ferritin (the hepcidin/ferritin ratio). Conclusions: The results suggest a mutual control of serum hepcidin and ferritin concentrations, a mechanism relevant to the pathophysiology of HFE haemochromatosis, and demonstrate that the HFE rs1800562 C282Y variant exerts a direct pleiotropic effect on the iron parameters, in part independent of hepcidin.
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Serum hepcidin measurement does not provide any information additional to serum ferritin, since the two variables are tightly related.
“However, this does not provide any information additional to serum ferritin, since the two variables are tightly related.112,113”
From Iron metabolism and iron disorders revisited in the hepcidin era (2020) · cites this paper as [112]
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Cites
Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
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“Hepcidin controls the surface expression of the iron exporter ferroportin on enterocytes and iron recycling macrophages.(3) Genetic disorders of the hepcidineferroportin pathway lead to opposite conditions.”
BackgroundGenABEL: an R library for genome-wide association analysis
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Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway
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Iron metabolism and iron disorders revisited in the hepcidin era
Camaschella, C., Nai, A., & Silvestri, L. (2020) · Haematologica · doi:10.3324/haematol.2019.232124 · Cited by 734 · see citing works
Self-citationCamaschella, C. (2019) · Blood · doi:10.1182/blood-2018-05-815944 · Cited by 702 · see citing works
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Self-citationDeletion of TMPRSS6 attenuates the phenotype in a mouse model of β-thalassemia
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Serum Hepcidin in Inflammatory Bowel Diseases: Biological and Clinical Significance
Bergamaschi, G., Di Sabatino, A., Albertini, R., Costanzo, F., Guerci, M., Masotti, M., Pasini, A., Massari, A., Campostrini, N., Corbella, M., et al. (2013) · Inflammatory Bowel Diseases · doi:10.1097/mib.0b013e31829a6e43 · Cited by 56 · see citing works
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- Authors
- Traglia, M., Girelli, D., Biino, G., Campostrini, N., Corbella, M., Sala, C., Masciullo, C., Viganò, F., Buetti, I., Pistis, G., Cocca, M., Camaschella, C., & Toniolo, D.
- Affiliations
- IRCCS Ospedale San Raffaele (IT)
- University of Verona (IT)
- Istituto di Genetica Molecolare (IT)
- Vita-Salute San Raffaele University (IT)
- Corresponding author
- Toniolo, Daniela
- ORCID
- Venue
- Journal of Medical Genetics
- Publisher
- BMJ
- Published
- 2011-07-23
- Volume
- 48
- Issue
- 9
- Pages
- 629-634
- ISSN
- 0022-2593 (ISSN-L)
- 1468-6244
- OpenAlex
- W2155679596
- Cited by
- 97
- References
- 6
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 5 · 2021: 9 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 7 · 2016: 8 · 2015: 11 · 2014: 13 · 2013: 9 · 2012: 10
- FWCI
- 7.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Medical Genetics (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- hepcidin, HFE gene, iron homeostasis, ferritin, transferrin saturation, serum iron, red blood cell indices, genetic association, pleiotropy, age and sex differences
- MeSH terms
- Hemochromatosis Protein, Adolescent, Adult, Aged, Aged, 80 and over, Erythrocytes, Female, Ferritins, Humans, Iron, Male, Membrane Proteins, Middle Aged, Serine Endopeptidases, Genetic Variation, Histocompatibility Antigens Class I, Antimicrobial Cationic Peptides, Young Adult, Hepcidins
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