HFE (haemochromatosis)

rs1800562 · rs1799945

HFE variants disturb the regulation of iron uptake in the gut. The C282Y variant is the main cause of hereditary haemochromatosis: homozygous carriers can store too much iron over years. The variant is common, the disease rarer thanks to incomplete penetrance, and well treatable.

The two variants

C282Y (rs1800562) destroys a disulfide bond in the HFE protein and thus disturbs its function most strongly. H63D (rs1799945) is a milder amino acid change. Only certain combinations, above all C282Y in double form, markedly raise the risk of relevant iron overload.

Why early detection is valuable

Excess iron deposits in liver, heart and joints and can cause damage there. Detected early, treatment is simple and effective: regular phlebotomy lowers the iron store. This makes HFE one of the few consumer markers with a clear, actionable consequence.

Context

The genotype is a hint, not a diagnosis. Whether iron overload is actually present is shown by iron parameters in blood. Genome presents the genotype and leaves assessment and consequence to the physician.

What Genome measures. The genotypes at rs1800562 (C282Y) and rs1799945 (H63D) and the resulting haemochromatosis risk constellation.

Related topics

rsIDs, microarray and SNP lookupDisease associations

Sources

  1. 1Feder et al., 1996 A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature Genetics 13:399–408. doi.org/10.1038/ng0896-399
  2. 2EASL, 2010 EASL clinical practice guidelines for HFE hemochromatosis. Journal of Hepatology 53:3–22. doi.org/10.1016/j.jhep.2010.03.001