Editing Hereditary haemochromatosis (section)

== Epidemiology ==
Haemochromatosis is one of the most common heritable genetic conditions in people of [[Northern Europe]], with a prevalence of 1:200.<ref name=":1">{{Cite journal|date=14 June 2021|title=Hemochromatosis|website=Medscape|url=https://emedicine.medscape.com/article/177216-overview#a6|access-date=20 November 2021|archive-date=22 May 2023|archive-url=https://web.archive.org/web/20230522141325/https://emedicine.medscape.com/article/177216-overview#a6|url-status=live}}</ref> The disease has a variable penetration, and about one in 10 people of this demographic carry a mutation in one of the genes regulating iron metabolism.<ref name="pmid18762941">{{cite journal |vauthors=Mendes AI, Ferro A, Martins R, etal |s2cid=23206256 |title=Non-classical hereditary hemochromatosis in Portugal: novel mutations identified in iron metabolism-related genes |journal=Ann. Hematol. |volume=88 |issue=3 |pages=229–34 |date=March 2009 |pmid=18762941 |doi=10.1007/s00277-008-0572-y |url=https://hal.archives-ouvertes.fr/hal-00477968/file/PEER_stage2_10.1007%252Fs00277-008-0572-y.pdf |access-date=29 August 2019 |archive-date=29 August 2019 |archive-url=https://web.archive.org/web/20190829095718/https://hal.archives-ouvertes.fr/hal-00477968/file/PEER_stage2_10.1007%25252Fs00277-008-0572-y.pdf |url-status=live }}</ref> In the [[U.S.]], the frequency of the [[HFE (gene)|C282Y]] and [[HFE H63D gene mutation|H63D]] mutations is 5.4% and 13.5%, respectively. Whereas, the worldwide frequency of the C282Y and H63D mutations is about 1.9% and 8.1%, respectively, so mutation in H63D allele are more than C282Y allele.<ref name=":1" /> The [[prevalence]] of mutations in iron-metabolism genes varies in different populations.  A study of 3,011 unrelated white Australians found that 14% were [[heterozygous]] carriers of an HFE mutation, 0.5% were [[homozygous]] for an ''HFE'' mutation, and only 0.25% of the study population had clinically relevant iron overload.  Most patients who are [[homozygous]] for ''HFE'' mutations do not manifest clinically relevant haemochromatosis (see Genetics above).<ref name=Olynwk_1999>{{cite journal |vauthors=Olynyk J, Cullen D, Aquilia S, Rossi E, Summerville L, Powell L |title=A population-based study of the clinical expression of the hemochromatosis gene |journal=N Engl J Med |volume=341 |issue=10 |pages=718–24 |year=1999 |pmid=10471457 |doi=10.1056/NEJM199909023411002 |url=http://researchrepository.murdoch.edu.au/id/eprint/18788/1/population_based_study.pdf |access-date=5 April 2019 |archive-date=10 August 2017 |archive-url=https://web.archive.org/web/20170810041855/http://researchrepository.murdoch.edu.au/id/eprint/18788/1/population_based_study.pdf |url-status=live }}</ref> Other populations have a lower prevalence of both the genetic mutation and the clinical disease. It is the most frequent genetic disease in the [[U.S.]] with a prevalence of 1:300 in the [[non-Hispanic white|non-Hispanic white population]],<ref name="Iron Overload and Hemochromatosis"/><ref>{{Cite journal |last1=McLaren |first1=Gordon D. |last2=Gordeuk |first2=Victor R. |date=January 2009 |title=Hereditary hemochromatosis: insights from the Hemochromatosis and Iron Overload Screening (HEIRS) Study |journal=Hematology |volume=2009 |issue=1 |pages=195–206 |doi=10.1182/asheducation-2009.1.195 |doi-access=free|pmid=20008199 |pmc=3829617 }}</ref> It is 2–3 times more common in males.<ref name=YY>{{Cite book | title=StatPearls | chapter=Hemochromatosis | year=2021 | publisher=StatPearls | pmid=28613612 | last1=Porter | first1=J. L. | last2=Rawla | first2=P. | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK430862/ | access-date=22 May 2021 | archive-date=27 January 2022 | archive-url=https://web.archive.org/web/20220127040343/https://www.ncbi.nlm.nih.gov/books/NBK430862/ | url-status=live }}</ref>

[[Genetics]] studies suggest the original haemochromatosis mutation arose in a single person, possibly of Celtic ethnicity, who lived 60–70 generations ago.<ref>{{cite journal |url=http://www.scripps.edu/bcmd/pdfarea/issue_20_98/lucotte.pdf |last=Lucotte |first=Gérard |date=1998-10-31 |title=Celtic Origin of the C282Y Mutation of Hemochromatosis |journal=Blood Cells, Molecules and Diseases |volume=24 |issue=20 |pages=433–438 |doi=10.1006/bcmd.1998.0212 |pmid=9851897 |issn=1079-9796 |access-date=7 January 2014 |archive-url=https://web.archive.org/web/20081202181211/http://www.scripps.edu/bcmd/pdfarea/issue_20_98/lucotte.pdf |archive-date=2 December 2008 }}</ref> At that time, when dietary iron may have been scarcer than today, the presence of the [[mutant allele]] may have provided an [[evolution]]ary advantage by maintaining higher iron levels in the blood.{{citation needed|date=March 2022}}

The distribution of the C282Y variant was noted in various countries. Non-HFE associated hemochromatosis, as [[Juvenile hemochromatosis|Haemochromatosis type 2]], [[Haemochromatosis type 3]], [[Haemochromatosis type 4]] and Haemochromatosis type 5,<ref name="J" /> were discovered in Mediterranean countries. On the other side, Northern European ancestry is closely linked to hereditary hemochromatosis disease (HFE). In one study, over 93% of Irish patients with HFE C282Y mutation were homozygotic. The G320V mutation in the HJV gene, which produces [[hemojuvelin]] protein, is widely distributed in central Europe and Greece.<ref name=":1"/>