Iron Overloading; Of Genetic Origin
Genetic Variant: mutation that affects the regulation of absorption and storage of iron, resulting in higher amounts of iron absorption and less protection against iron overload.
This genetic variation can involve several separate genes. The HFE protein has “common variants that promote iron absorption”.1 One of these variants occurs at position 282 in the HFE protein where a substitution of tyrosine for the regular cysteine takes place.1 The resulting effects are symptoms congruent with the diagnosis of type 1 hemochromatosis which produces toxic overloading of iron.2 Unoccupied iron in the body oxidizes and wreaks havoc on the system as a mischievous free radical. Ultimately this condition is dangerous and left untreated can be deadly.
Properly functioning HFE controls the production Hepcidin, also a protein.2 Hepcidin’s function as a hormone is necessary for the body’s regulatory power of iron absorption.2 Hepcidin is made by the liver and not only decides how much iron is allowed to be absorbed from the enterocytes, but also decides the proper amount of iron to be mobilized from stores in the liver when required.2 This tight regulation helps fend of deficiency while simultaneously protecting from toxicity, as iron requires such tight regulation. Homeostasis is not the sole function of this protein, which is also active in innate immunity.3
The precise mechanism that allows a flooding of iron into the system is a direct result of the variant described above. The substitution of amino acids on the HFE protein, or genetic variant, is coined “Cys282Tyr”.2 Without the proper function of HFE, iron is free to flood the system in unhealthy amounts in Hepcidin’s absence. Over-accumulation of iron in the system can result in neurotoxicity, and is currently being studied as a precursor in those with neurodegenerative diseases.3
Another variant on the same protein, H63D (HFE), has been shown to be a viable marker for ALS.3 In another study HFE is suspected to be a part of the multifactorial predispositions of type 2 diabetes.4 This study admits that it may play a role in predisposing someone to diabetes, but does not act alone as a causation.
1. Martin Kohlmeier. Nutrigenetics, (Applying the Science of Personal Nutrition). First. Elsevier; 2013.
2. Reference GH. HFE gene. Genetics Home Reference. https://ghr.nlm.nih.gov/gene/HFE. Accessed April 28, 2017.
3. Nandar W, Connor JR. HFE Gene Variants Affect Iron in the Brain. J Nutr. 2011;141(4):729S-739S. doi:10.3945/jn.110.130351.
4. Barton JC, Acton RT. Diabetes in HFE Hemochromatosis. J Diabetes Res. 2017;2017. doi:10.1155/2017/9826930.