title: Decreased iron burden in overweight C282Y homozygous women: Putative role of increased hepcidin production.
abstract: An excess of visceral adipose tissue could be involved as a modulator of the penetrance of HFE hemochromatosis since fat mass is associated with overexpression of hepcidin and low transferrin saturation was found to be associated with being overweight in women. This study was aimed at assessing the relationship between body mass index (BMI), a surrogate marker of insulin resistance, and iron burden in HFE hemochromatosis. In all, 877 patients from a cohort of C282Y homozygotes were included in the study when BMI at diagnosis and amount of iron removed (AIR) by phlebotomy were available. No relationship between AIR and BMI was found in men, whereas 15.1% (52/345) of women with AIR <6 g had BMI ≥28 versus 3.9% (2/51) of women with AIR ≥6 g (P = 0.03). At multivariate analysis, BMI was an independent factor negatively associated with AIR (odds ratio: 0.13; 95% confidence interval [CI]: 0.03-0.71) together with serum ferritin, serum transferrin, transferrin saturation, hemoglobin, and alanine aminotransferase. In a control group of 30 C282Y homozygous women, serum hepcidin was significantly higher in overweight (14.3 mmoL/L ± 7.1) than in lean (7.9 mmoL/L ± 4.3) women (P = 0.0005).
  
  
  CONCLUSIONS
  In C282Y homozygous women, BMI ≥28 kg/m(2) is independently associated with a lower amount of iron removed by phlebotomy. BMI is likely a modulator factor of the phenotypic expression of C282Y homozygosity, likely through an increase of circulating levels of hepcidin.
authors: CHU Rennes, Service des maladies du foie, Rennes, France.
authors: Romain
authors: R
authors: Desgrippes
authors: Fabrice
authors: F
authors: Lainé
authors: Jeff
authors: J
authors: Morcet
authors: Michèle
authors: M
authors: Perrin
authors: Ghislain
authors: G
authors: Manet
authors: Caroline
authors: C
authors: Jezequel
authors: Edouard
authors: E
authors: Bardou-Jacquet
authors: Martine
authors: M
authors: Ropert
authors: Yves
authors: Y
authors: Deugnier
mesh_terms: D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D015992:Body Mass Index; D016022:Case-Control Studies; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D005293:Ferritins / Q000097:blood; D006432:Hemochromatosis / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D007501:Iron / Q000097:blood*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D050177:Overweight / Q000097:blood* / Q000453:epidemiology; D018962:Phlebotomy; D012189:Retrospective Studies; D014168:Transferrin / Q000378:metabolism
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; D014168:Transferrin; D005293:Ferritins; D007501:Iron