Abstract
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.
Highlights
Humans are able to modify the surrounding environment by exploiting progressively advanced technologies, with the purpose to derive water, nourishment, energy and shelter
Several lines of evidence indicate that ferritin levels and body iron stores should be considered as hallmarks of metabolic syndrome (MetS) whose key pathogenic feature is represented by insulin resistance (IR) [54,55,56]
We have recently demonstrated that iron challenge in iron-depleted dysmetabolic iron overload syndrome (DIOS) patients did not restrain iron absorption despite adequate hepcidin production, suggesting that hepcidin resistance and not the deficit of hormone production is involved in DIOS pathogenesis [81]
Summary
Humans are able to modify the surrounding environment by exploiting progressively advanced technologies, with the purpose to derive water, nourishment, energy and shelter. This process is defined as “niche construction” and may be profoundly influenced by behavioral and cultural traits [1]. Favorable mutations have been selected and expanded within ancient populations [4,5], which explains their high incidence in the modern ones. Such favorable genetic variants may become a modern-day candidate risk factor for several disorders, due to changes in environmental conditions. The present review aims to explore how environmental pressures lead to adaptive alterations of the genome through the selection of favorable mutations and whether it is possible to introduce dietary and lifestyle interventions in the management of iron-related hepatic disorders caused by selected inherited variations that have become maladaptive in the modern age
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
