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From SNPedia

Hereditary Hemochromatosis, also called HH, is an iron storage disorder (see the Hemochromatosis Information Center) where excess iron is not effectively removed from the blood. In serious cases, this excess iron will cause iron overload and if untreated can lead to cirrhosis of the liver, diabetes, hypermelanotic pigmentation of the skin, heart disease, liver cancer, depression, fatigue and other problems. These long-term complications can nearly always be avoided if the person is treated.

The terminology for this can be confusing. Those with two copies of Hereditary Hemochromatosis alleles will have very likely have some trouble processing iron, but won't necessarily have Hemochromatosis. Hemochromatosis is only diagnosed when blood iron levels exceed certain thresholds. Depending on which alleles you have and other factors, your iron processing deficiency may not reach the level of formally being diagnosed as Hemochromatosis. Women are less likely to have Hemochromatosis because menstruation will regularly eliminate excess iron, but may become affected after menopause. Similarly, regular blood donors are unlikely to be affected. Diet, alcohol consumption and supplement use all can affect blood iron levels.

Hemochromatosis is easily diagnosed through an iron panel of blood tests. If Hemochromatosis is diagnosed, it can be easily treated by phlebotomy or regular donation of blood to reduce blood iron levels. A low-iron diet can also help control build up of iron. Those affected should avoid vitamin supplements containing iron and also heavy vitamin C and alcohol consumption which can interfere with iron processing. Those with two copies of Hereditary Hemochromatosis who are diagnosed as not having Hemochromatosis should still familiarize themselves with the symptoms in case it develops later.

The following SNPs are associated with Hereditary Hemochromatosis. People with two copies of a risk allele have a higher chance of developing Hemochromatosis, but most do not or are mildly affected. Those with two Hereditary Hemochromatosis genes can take an iron panel of blood tests to see if they are affected. Carriers of a single copy are not affected by Hereditary Hemochromatosis.

  • rs1800562 in the HFE gene, also known as C282Y (risk genotype AA) can cause a serious form of Hemochromatosis, and accounts for about 85% of Hemochromatosis patients. About 1 in 200 people of European ancestry is a carrier of this mutation.
  • rs1799945 in the HFE gene, also known as H63D (risk genotype GG), can cause a mild form of Hemochromatosis.

Those who are carriers (one risk allele) of both the C282Y and H63D variants may be affected by a mild form of Hereditary Hemochromatosis, but only if they are on separate chromosomes (i.e. one is on the maternally inherited copy of the HFE gene, and the other is on the paternally inherited copy). Note that microarray based genotyping (such as is done by 23andMe or FamilyTreeDNA) cannot determine if the variants are on the same allele (i.e. chromosome).

Other SNPs may influence the risk of serious hemochromatosis:

  • rs235756 in the BMP2 gene may lead to higher risk of developing hemochromatosis in carriers of two A alleles of rs1800562.
  • rs1800730, called i3002468 by 23andMe, in the HFE gene, also known as S65C (risk allele T), may be associated with a third Hereditary Hemochromatosis variant, but more research is needed.

There are several types of hereditary hemochromatosis other than the classic (Type 1) form primarily being discussed in the preceding paragraphs. Type 2 hemochromatosis is the result of mutations in the HJV or the HAMP genes, while TFR2 gene mutations cause Type 3 hemochromatosis; like Type 1, Type 2 and Type 3 are recessively inherited conditions. In contrast, dominant mutations in the SLC40A1 gene can lead to Type 4 hemochromatosis.