Hereditary Hemochromatosis: Get your HFE status using DNA raw data

23andme Hemochromatosis status can be used to identify a hereditary condition in which the body absorbs the excess of iron from the food consumed. Iron is important for various functions like oxygen transport and for oxidative phosphorylation. While iron deficiency can lead to anemia, excessive iron can lead to iron-overload. The iron levels in the body can be determined by evaluating serum iron levels, serum transferrin and saturation of transferrin with iron. It has been estimated that 25 to 50% variation in these blood iron markers is due to genetic variants carried by an individual.

Normally about 8 to 10% of iron from food is absorbed in the body, however, in people with hemochromatosis, there is 4 times increase in absorption. This condition of iron overload is also known as genetic hemochromatosis and leads to the slow accumulation of iron which can eventually lead to organ damage. DNA raw data can be used to check for variants in the hemochromatosis gene, C282Y and H36D.

Evolutionary origin of hemochromatosis gene mutation:

Genetic variants to specific traits are inherited due to an environmental pressure that either triggered the mutation or which encouraged people with the variants to survive. Evolutionary biologists believe that this condition arose as a result of low iron reserves from food in the Celtic region, about 6000 years ago, which necessitated storage of available iron from food. Though this variant was beneficial during the period of poor iron reserves and when the risk of maternal iron deficiency was high, this condition can lead to serious health effects now, if left undetected.

What are hereditary hemochromatosis symptoms?

Hereditary hemochromatosis is present from birth, as it is caused due to the presence of a genetic variant. However, most people with this condition exhibit symptoms only during middle age. Men are more likely to show symptoms at an earlier age, in their 30s. Women begin to show symptoms only postmenopause, when they no longer lose iron during their monthly menstruation or during pregnancy.

The symptoms are usually mild or remain undetected as most of the symptoms are similar to common conditions. Hereditary hemochromatosis symptoms include

Abdominal pain
Joint pain
Weakness
Fatigue
Abnormal skin colour
Hypothyroidism
Hypogonadism
Diabetes
Heart failure
Liver failure

How do hemochromatosis gene variants lead to iron overload?

The liver secretes a hormone called hepcidin which is responsible for maintaining iron levels in the body, how much is absorbed and where it is stored. Certain genetic variants in the hemochromatosis gene disrupt the functioning of hepcidin and result in excessive absorption of iron from the food consumed. This excess iron is then stored in the liver and other major organs. Over a prolonged period of time, the excess of iron in such organs can lead to organ failure, diabetes or heart failure.

How do you find out your 23andme hemochromatosis status?

Upload your DNA raw data from 23andme to find out your hemochromatosis status. There are essentially two significant genetic variants in the HFE gene associated with hemochromatosis.

c282Y (rs1800562)
H63D (rs1799945)

Significant of the two is C282Y, people who carry two AA are associated with a higher risk for hemochromatosis. According to a study published in the American Journal of Human Genetics, the C282Y variant contributes to 26% variation in ferritin levels among monozygotic twins and 20% phenotypic variation.

Using DNA raw data to find your hemochromatosis status

Upload your 23andme or your Ancestry DNA raw data to find which variants of rs1800562 you carry

Genotype	Phenotype
AA	[Limitation] Likely higher risk for hemochromatosis
AG	[Limitation] Likely moderate risk for hemochromatosis
GG	[Advantage] Likely normal

Upload your 23andme or your Ancestry DNA raw data to find which variants of rs1799945 you carry

Genotype	Phenotype
GG	[Limitation] Likely higher risk for mild hemochromatosis
CG	[Limitation] Likely moderate risk for mild hemochromatosis
CC	[Advantage] Likely normal

Who is a hemochromatosis carrier?

A person who has one risk variant of rs1800562 and one normal variant is considered to be a carrier. Approximately 1 in 10 Americans carry one copy of this variant and are carriers.

Compound heterozygous: People who carry one risk variant of rs1800562 and one risk variant on rs1799945 have a higher risk of developing hemochromatosis if the variants are on separate chromosomes, one from the father and the other from the mother.

What are the different types of hemochromatosis?

Apart from hereditary hemochromatosis, there are other hemochromatosis conditions that can lead to iron overload.

Juvenile hemochromatosis: This condition occurs earlier than classic hereditary hemochromatosis. It occurs due to mutations in the hepcidin gene.
Secondary hemochromatosis: Excessive blood transfusions during certain disease conditions, like liver disease, could result in iron overload
Neonatal hemochromatosis: This is considered to be an autoimmune condition that leads to a build up of iron among neonates.

Will everyone with the hemochromatosis HFE C282Y variant develop iron overload?

Nearly 1 in 200 Americans carry two copies of the A variant of C282Y, which increases their risk for hemochromatosis. Not everyone who carries two copies of this variant develops hemochromatosis, only about 10 % develops iron overload. Early identification of the genetic variant carried will help in managing this condition and help prevent tissue damage due to excess iron.

How will knowing more about your 23andme hemochromatosis status help?

Identifying the genetic variant carried will help in altering lifestyle and dietary habits to prevent excess iron in the body, specifically in organs and tissues.

The following are some important ways to manage hemochromatosis

Phlebotomy: One of the most effective methods of managing high levels of iron in the blood or for those who have a high risk is to donate blood every 6 months under medical supervision. This will help in preventing excess of iron build up in the body.
Moderate consumption of iron rich foods: Red meat or meat from venison, goat, pork or beef are rich in iron and should be avoided. Cereals and snacks that are fortified with iron should also not be consumed by high risk men and older women.
Consume black tea: Drinking a cup of black tea along with meals lowers absorption of iron from the food consumed.
Watch out for bacterial infections: Gram negative bacteria thrive in iron rich substrates and oysters and other seafood are known to host such bacteria. Therefore consumption of such seafood should be avoided.
Limit intake of alcohol: Hemochromatosis individuals who show signs of liver damage should avoid intake of alcohol.
Moderate intake of vitamin A and Vitamin C rich foods: Vitamin A and Vitamin C upregulate iron absorption and should, therefore, be consumed in moderation.