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

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 cha...

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Autores principales: Rametta, Raffaela, Meroni, Marica, Dongiovanni, Paola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279025/
https://www.ncbi.nlm.nih.gov/pubmed/32429125
http://dx.doi.org/10.3390/ijms21103505
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author Rametta, Raffaela
Meroni, Marica
Dongiovanni, Paola
author_facet Rametta, Raffaela
Meroni, Marica
Dongiovanni, Paola
author_sort Rametta, Raffaela
collection PubMed
description 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.
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spelling pubmed-72790252020-06-15 From Environment to Genome and Back: A Lesson from HFE Mutations Rametta, Raffaela Meroni, Marica Dongiovanni, Paola Int J Mol Sci Review 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. MDPI 2020-05-15 /pmc/articles/PMC7279025/ /pubmed/32429125 http://dx.doi.org/10.3390/ijms21103505 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Rametta, Raffaela
Meroni, Marica
Dongiovanni, Paola
From Environment to Genome and Back: A Lesson from HFE Mutations
title From Environment to Genome and Back: A Lesson from HFE Mutations
title_full From Environment to Genome and Back: A Lesson from HFE Mutations
title_fullStr From Environment to Genome and Back: A Lesson from HFE Mutations
title_full_unstemmed From Environment to Genome and Back: A Lesson from HFE Mutations
title_short From Environment to Genome and Back: A Lesson from HFE Mutations
title_sort from environment to genome and back: a lesson from hfe mutations
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279025/
https://www.ncbi.nlm.nih.gov/pubmed/32429125
http://dx.doi.org/10.3390/ijms21103505
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