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Review

From Environment to Genome and Back: A Lesson from HFE Mutations

1
General Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pad. Granelli, via F Sforza 35, 20122 Milan, Italy
2
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122 Milan, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(10), 3505; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103505
Received: 10 April 2020 / Revised: 7 May 2020 / Accepted: 12 May 2020 / Published: 15 May 2020
(This article belongs to the Special Issue Nutrigenomics in Liver Diseases: An Uncharted Territory)
The environment and the human genome are closely entangled and many genetic variations that occur in human populations are the result of adaptive selection to ancestral environmental (mainly dietary) conditions. However, the selected mutations may become maladaptive when environmental conditions change, thus becoming candidates for diseases. Hereditary hemochromatosis (HH) is a potentially lethal disease leading to iron accumulation mostly due to mutations in the HFE gene. Indeed, homozygosity for the C282Y HFE mutation is associated with the primary iron overload phenotype. However, both penetrance of the C282Y variant and the clinical manifestation of the disease are extremely variable, suggesting that other genetic, epigenetic and environmental factors play a role in the development of HH, as well as, and in its progression to end-stage liver diseases. Alcohol consumption and dietary habits may impact on the phenotypic expression of HFE-related hemochromatosis. Indeed, dietary components and bioactive molecules can affect iron status both directly by modulating its absorption during digestion and indirectly by the epigenetic modification of genes involved in its uptake, storage and recycling. Thus, the premise of this review is to discuss how environmental pressures led to the selection of HFE mutations and whether nutritional and lifestyle interventions may exert beneficial effects on HH outcomes and comorbidities. View Full-Text
Keywords: Hereditary hemochromatosis; HFE; iron metabolism; polyphenols; vitamins; miRNAs; insulin signaling Hereditary hemochromatosis; HFE; iron metabolism; polyphenols; vitamins; miRNAs; insulin signaling
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MDPI and ACS Style

Rametta, R.; Meroni, M.; Dongiovanni, P. From Environment to Genome and Back: A Lesson from HFE Mutations. Int. J. Mol. Sci. 2020, 21, 3505. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103505

AMA Style

Rametta R, Meroni M, Dongiovanni P. From Environment to Genome and Back: A Lesson from HFE Mutations. International Journal of Molecular Sciences. 2020; 21(10):3505. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103505

Chicago/Turabian Style

Rametta, Raffaela, Marica Meroni, and Paola Dongiovanni. 2020. "From Environment to Genome and Back: A Lesson from HFE Mutations" International Journal of Molecular Sciences 21, no. 10: 3505. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103505

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