Editing Iron overload (section)

==Epidemiology==

HH type 1 is most common in certain European populations (such as those of Irish or Scandinavian descent) and occurs in 0.6% of that population.<ref name=AFP2013/> Men have a 24-fold increased rate of iron-overload disease compared with women.<ref name=AFP2013/>

===Stone Age===
Diet and the environment are thought to have had large influence on the mutation of genes related to iron overload. Starting during the [[Mesolithic era]], communities of people lived in an environment that was fairly sunny, warm and had the dry climates of the Middle East. Most humans who lived at that time were foragers and their diets consisted largely of wild plants, fish, and game. Archaeologists studying [[dental plaque]] have found evidence of [[tuber]]s, nuts, [[Cooking banana|plantains]], grasses and other foods rich in iron. Over many generations, the human body became well-adapted to a high level of iron content in the diet.<ref>{{Cite news|url=https://www.nationalgeographic.com/foodfeatures/evolution-of-diet/|title=The Evolution of Diet|work=National Geographic|access-date=2018-04-11}}</ref>

=== Neolithic ===
In the [[Neolithic era]], significant changes are thought to have occurred in both the environment and diet. Some communities of foragers migrated north, leading to changes in lifestyle and environment, with a decrease in temperatures and a change in the landscape which the foragers then needed to adapt to. As people began to develop and advance their tools, they learned new ways of producing food, and [[History of agriculture|farming also slowly developed]]. These changes would have led to serious stress on the body and a decrease in the consumption of iron-rich foods. This transition is a key factor in the mutation of genes, especially those that regulated dietary iron absorption. 70% of the body’s iron is found in the [[red blood cell|red blood cells]] and it is a critical [[micronutrient]] for effective [[thermoregulation]] in the body.<ref>{{Cite journal|last1=Rosenzweig|first1=P. H.|last2=Volpe|first2=S. L.|date=March 1999|title=Iron, thermoregulation, and metabolic rate|journal=Critical Reviews in Food Science and Nutrition|volume=39|issue=2|pages=131–148|doi=10.1080/10408399908500491|issn=1040-8398|pmid=10198751}}</ref> Iron deficiency will lead to a drop in the core temperature. In the chilly and damp environments of Northern Europe, supplementary iron from food was necessary to keep temperatures regulated, however, without sufficient iron intake the human body would have started to store iron at higher rates than normal. In theory, the pressures caused by migrating north would have selected for a [[gene mutation]] that promoted greater absorption and storage of iron.<ref>
{{Cite journal|last1=Heath|first1=Kathleen M.|last2=Axton|first2=Jacob H.|last3=McCullough|first3=John M.|last4=Harris|first4=Nathan|date=May 2016|title=The evolutionary adaptation of the C282Y mutation to culture and climate during the European Neolithic|journal=American Journal of Physical Anthropology|volume=160|issue=1|pages=86–101|doi=10.1002/ajpa.22937|issn=0002-9483|pmc=5066702|pmid=26799452}}
</ref>

===Viking hypothesis===
Studies and surveys conducted to determine the frequencies of hemochromatosis help explain how the mutation migrated around the globe. In theory, the disease initially evolved from travelers migrating from the north. Surveys show a particular distribution pattern with large clusters and frequencies of gene mutations along the western European coastline.<ref>{{Cite web|url=http://www.hematology.org/Thehematologist/Diffusion/6103.aspx|title=Clinical Penetrance of HFE Hereditary Hemochromatosis, Serum Ferritin Levels, and Screening Implications: Can We Iron This Out?|date=2008-05-01|website=www.hematology.org|access-date=2018-04-11|archive-date=2018-06-15|archive-url=https://web.archive.org/web/20180615135540/http://www.hematology.org/Thehematologist/Diffusion/6103.aspx|url-status=dead}}</ref> This led the development of the "[[Viking]] Hypothesis".<ref>{{Cite journal|last1=Symonette|first1=Caitlin J|last2=Adams|first2=Paul C|date=June 2011|title=Do all hemochromatosis patients have the same origin? A pilot study of mitochondrial DNA and Y-DNA|journal=Canadian Journal of Gastroenterology|volume=25|issue=6|pages=324–326|issn=0835-7900|pmc=3142605|pmid=21766093|doi=10.1155/2011/463810|doi-access=free}}
</ref> Cluster locations and mapped patterns of this mutation correlate closely to the locations of [[Viking expansion|Viking settlements in Europe]] established c.700 AD to c.1100 AD. The Vikings originally came from Norway, Sweden and Denmark. [[Viking ships]] made their way along the coastline of Europe in search of trade, riches, and land. Genetic studies suggest that the extremely high frequency patterns in some European countries are the result of migrations of Vikings and later [[Normans]], indicating a genetic link between hereditary hemochromatosis and Viking ancestry.<ref name=":2">{{Cite web|url=https://www.toomuchiron.ca/video/|title=Videos: Hereditary Hemochromatosis {{!}} Canadian Hemochromatosis Society|website=www.toomuchiron.ca|access-date=2018-04-11|archive-date=2018-04-11|archive-url=https://web.archive.org/web/20180411174723/https://www.toomuchiron.ca/video/|url-status=dead}}</ref>

===Modern times===
In 1865, [[Armand Trousseau]] (a French internist) was one of the first to describe many of the symptoms of a diabetic patient with cirrhosis of the liver and bronzed skin color. The term hemochromatosis was first used by German pathologist [[Friedrich Daniel von Recklinghausen]] in 1889 when he described an accumulation of iron in body tissues.<ref name=":0">{{Cite journal|last1=Fitzsimons|first1=Edward J.|last2=Cullis|first2=Jonathan O.|last3=Thomas|first3=Derrick W.|last4=Tsochatzis|first4=Emmanouil|last5=Griffiths|first5=William J. H.|last6=the British Society for Haematology|date=May 2018|title=Diagnosis and therapy of genetic haemochromatosis (review and 2017 update)|journal=British Journal of Haematology|language=en|volume=181|issue=3|pages=293–303|doi=10.1111/bjh.15164|pmid=29663319|doi-access=free}}</ref>