title: Association of HFE and TMPRSS6 genetic variants with iron and erythrocyte parameters is only in part dependent on serum hepcidin concentrations.
abstract: BACKGROUND
  Hepcidin is the main regulator of iron homeostasis: inappropriate production of hepcidin results in iron overload or iron deficiency and anaemia.
  
  
  OBJECTIVE
  To study variation of serum hepcidin concentration in a normal population.
  
  
  RESULTS
  Hepcidin showed age and sex dependent variations that correlated with ferritin but not with serum iron and transferrin saturation. The size of the study population was underpowered to find genome wide significant associations with hepcidin concentrations but it allowed to show that association with serum iron, transferrin saturation and erythrocyte traits of common DNA variants in HFE (rs1800562) and TMPRSS6 (rs855791) genes is not exclusively dependent on hepcidin values. When multiple interactions between environmental factors, the iron parameters and hepcidin were taken into account, the HFE variant, and to lesser extent the TMPRSS6 variant, were associated with ferritin and with hepcidin normalised to ferritin (the hepcidin/ferritin ratio).
  
  
  CONCLUSIONS
  The results suggest a mutual control of serum hepcidin and ferritin concentrations, a mechanism relevant to the pathophysiology of HFE haemochromatosis, and demonstrate that the HFE rs1800562 C282Y variant exerts a direct pleiotropic effect on the iron parameters, in part independent of hepcidin.
authors.affiliation: Division of Genetics and Cell Biology, San Raffaele Research Institute, Milano, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Traglia
authors.forename: Domenico
authors.initials: D
authors.lastname: Girelli
authors.forename: Ginevra
authors.initials: G
authors.lastname: Biino
authors.forename: Natascia
authors.initials: N
authors.lastname: Campostrini
authors.forename: Michela
authors.initials: M
authors.lastname: Corbella
authors.forename: Cinzia
authors.initials: C
authors.lastname: Sala
authors.forename: Corrado
authors.initials: C
authors.lastname: Masciullo
authors.forename: Fiammetta
authors.initials: F
authors.lastname: Viganò
authors.forename: Iwan
authors.initials: I
authors.lastname: Buetti
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pistis
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cocca
authors.forename: Clara
authors.initials: C
authors.lastname: Camaschella
authors.forename: Daniela
authors.initials: D
authors.lastname: Toniolo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005293:Ferritins / Q000097:blood; D014644:Genetic Variation; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000097:blood*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D012697:Serine Endopeptidases / Q000235:genetics*; D055815:Young Adult
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins; D007501:Iron; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human