From Environment to Genome and Back: A Lesson from <i>HFE</i> 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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MDPI AG
2020-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/10/3505 |
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| author | Raffaela Rametta Marica Meroni Paola Dongiovanni |
| author_facet | Raffaela Rametta Marica Meroni Paola Dongiovanni |
| author_sort | Raffaela Rametta |
| collection | DOAJ |
| 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 <i>HFE</i> gene. Indeed, homozygosity for the C282Y <i>HFE</i> 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 <i>HFE</i>-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 <i>HFE</i> mutations and whether nutritional and lifestyle interventions may exert beneficial effects on HH outcomes and comorbidities. |
| first_indexed | 2024-03-10T19:49:01Z |
| format | Article |
| id | doaj.art-d5096d0edc4342d1be424eef61075ecf |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:49:01Z |
| publishDate | 2020-05-01 |
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| spelling | doaj.art-d5096d0edc4342d1be424eef61075ecf2023-11-20T00:34:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-012110350510.3390/ijms21103505From Environment to Genome and Back: A Lesson from <i>HFE</i> MutationsRaffaela Rametta0Marica Meroni1Paola Dongiovanni2General Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pad. Granelli, via F Sforza 35, 20122 Milan, ItalyGeneral Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pad. Granelli, via F Sforza 35, 20122 Milan, ItalyGeneral Medicine and Metabolic Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pad. Granelli, via F Sforza 35, 20122 Milan, ItalyThe 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 <i>HFE</i> gene. Indeed, homozygosity for the C282Y <i>HFE</i> 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 <i>HFE</i>-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 <i>HFE</i> mutations and whether nutritional and lifestyle interventions may exert beneficial effects on HH outcomes and comorbidities.https://www.mdpi.com/1422-0067/21/10/3505Hereditary hemochromatosisHFEiron metabolismpolyphenolsvitaminsmiRNAs |
| spellingShingle | Raffaela Rametta Marica Meroni Paola Dongiovanni From Environment to Genome and Back: A Lesson from <i>HFE</i> Mutations International Journal of Molecular Sciences Hereditary hemochromatosis HFE iron metabolism polyphenols vitamins miRNAs |
| title | From Environment to Genome and Back: A Lesson from <i>HFE</i> Mutations |
| title_full | From Environment to Genome and Back: A Lesson from <i>HFE</i> Mutations |
| title_fullStr | From Environment to Genome and Back: A Lesson from <i>HFE</i> Mutations |
| title_full_unstemmed | From Environment to Genome and Back: A Lesson from <i>HFE</i> Mutations |
| title_short | From Environment to Genome and Back: A Lesson from <i>HFE</i> Mutations |
| title_sort | from environment to genome and back a lesson from i hfe i mutations |
| topic | Hereditary hemochromatosis HFE iron metabolism polyphenols vitamins miRNAs |
| url | https://www.mdpi.com/1422-0067/21/10/3505 |
| work_keys_str_mv | AT raffaelarametta fromenvironmenttogenomeandbackalessonfromihfeimutations AT maricameroni fromenvironmenttogenomeandbackalessonfromihfeimutations AT paoladongiovanni fromenvironmenttogenomeandbackalessonfromihfeimutations |