Modifying factors of the HFE hemochromatosis phenotype

Expert Rev Gastroenterol Hepatol. 2008 Aug;2(4):531-40. doi: 10.1586/17474124.2.4.531.

Abstract

C282Y homozygosity is the only common HFE genotype able to produce a complete hemochromatosis phenotype. However, its biochemical penetrance is incomplete (75% in men and 50% in women) and its clinical penetrance is low, especially in women (1 vs 25% in men). Environmental (e.g., diet, alcohol, drugs and metabolic syndrome) and genetic (digenism, common polymorphisms in the bone morphogenetic protein pathway involved in the regulation of hepcidin synthesis) explain a part of the variability of the C282Y homozygous phenotype. All other common HFE genotypes--including C282Y-H63D compound heterozygosity--are not associated with significant biochemical and clinical expression in the absence of comorbid factors (e.g., alcohol, diabetes or steatohepatitis). Better identification of acquired and genetic modifiers of iron burden and iron-related organ damage is needed to improve the preventive, diagnostic and therapeutic management of HFE hemochromatosis.

MeSH terms

  • Female
  • Genotype
  • Hemochromatosis / genetics*
  • Hemochromatosis / metabolism
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Iron / metabolism
  • Male
  • Membrane Proteins / genetics*
  • Phenotype*

Substances

  • HFE protein, human
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Iron