What genetic variants increase the risk of hemochromatosis?

Specific changes in the HFE gene are associated with an increased risk of hemochromatosis.

•  C282Y
•  H63D
•  S65C

C282Y is the most common mutation, and is associated with the most severe symptoms.

H63D and S65C are two other mutations that can increase the risk of hemochromatosis. However, often other precipitating factors (e.g. hepatitis or alcohol abuse) are also required before iron overload occurs.

To be at an increased risk of hemochromatosis, two defective copies of the HFE gene need to be inherited. Carriers, who have one normal and one defective HFE gene, are generally unaffected.