title: Hepatic iron metabolism gene expression profiles in HFE associated hereditary hemochromatosis.
abstract: BACKGROUND
  Individuals with pathogenic mutations in HFE, hemojuvelin (HJV) and transferrin receptor 2 (TfR2) have low levels of hepcidin, but little is known about the hepatic expression of these molecules in patients with physiological iron overload or HFE associated Hemochromatosis (HH).
  
  
  OBJECTIVE
  To examine the hepatic mRNA expression of iron homeostasis genes in patients with HH, physiological iron overload and healthy controls.
  
  
  METHODS
  Untreated C282Y homozygous HH patients (n=20) with elevated serum ferritin (SF) and patients with physiological iron overload (n=12) with positive hepatocellular iron staining and negative HFE mutation analysis were evaluated. The control cohort (n=10) had normal iron parameters, negative HFE mutation analysis and negative hepatocellular iron staining.
  
  
  METHODS
  Hepcidin, HJV (hemojuvelin), TfR2 (transferrin receptor 2), HFE, IL6 (interleukin 6) and ferroportin mRNA expression patterns were evaluated using quantitative real-time PCR.
  
  
  RESULTS
  Physiological iron overload led to significantly upregulated hepcidin, HJV and ferroportin mRNA expression while TfR2 expression was not significantly different to controls. In contrast, HFE associated iron overload failed to induce hepcidin or HJV. TfR2 mRNA expression was significantly reduced when compared to controls. Ferroportin expression in HH was comparable to that found in physiological iron overload. Neither HFE nor IL6 expression was altered by variation in iron status.
  
  
  CONCLUSIONS
  These findings suggest that patients with HH, in contrast to those with physiological iron overload, have a weakened TfR2 sensing mechanism that leads to the lack of induction of hepcidin and HJV. The C282Y HFE mutation does not appear to impede the hepatocellular iron export function of ferroportin.
authors.affiliation: Centre for Liver Disease, Mater Misericordiae University Hospital, Dublin 7, Ireland.
authors.forename: Ferga
authors.initials: F
authors.lastname: Gleeson
authors.forename: Eleanor
authors.initials: E
authors.lastname: Ryan
authors.forename: Sharon
authors.initials: S
authors.lastname: Barrett
authors.forename: Jennifer
authors.initials: J
authors.lastname: Russell
authors.forename: John
authors.initials: J
authors.lastname: Crowe
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling; D006432:Hemochromatosis / Q000235:genetics* / Q000378:metabolism*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D007501:Iron