Abstract
Inadequate hepcidin synthesis leads to iron overload in HFE-related hemochromatosis. We explored the regulation of hepcidin by iron in 88 hemochromatosis patients (61 C282Y/C282Y, 27 C282Y/H63D) and 23 healthy controls by analyzing urinary hepcidin before and 24 hours after a 65-mg oral iron dose. Thirty-four patients were studied at diagnosis and had iron overload, and 54 patients were iron depleted. At diagnosis, hepcidin values in C282Y homozygotes were similar to controls, whereas values in C282Y/H63D heterozygotes were higher (P = .02). However, the hepcidin/ferritin ratio was decreased in both homozygotes (P <.001) and heterozygotes (P = .017), confirming the inadequate hepcidin production for the iron load with both genotypes. In iron-depleted patients of both genotypes studied at a time remote from phlebotomy, basal hepcidin was still lower than in controls (P <.001 for C282Y/C282Y and P = .002 for heterozygotes). After an iron challenge, meanurinary hepcidin excretion increased in controls (P = .001) but not patients, irrespective of genotype and iron status. Significant hepcidin increase ( ≥ 10 ng/mg creatinine) was observed in 74%of controls,15% of homozygotes, and 32% of heterozygotes. The hepcidin response to oral iron is blunted in HFE-related hemochromatosis and not improved after iron depletion. The findings support the involvement of HFE in iron sensing and subsequent regulation of hepcidin.
| Original language | English |
|---|---|
| Pages (from-to) | 4096-4100 |
| Number of pages | 5 |
| Journal | Blood |
| Volume | 110 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 1 2007 |
Fingerprint
ASJC Scopus subject areas
- Hematology
Cite this
Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis. / Piperno, Alberto; Girelli, Domenico; Nemeth, Elizabeta; Trombini, Paola; Bozzini, Claudia; Poggiali, Erika; Phung, Yen; Ganz, Tomas; Camaschella, Clara.
In: Blood, Vol. 110, No. 12, 01.12.2007, p. 4096-4100.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis
AU - Piperno, Alberto
AU - Girelli, Domenico
AU - Nemeth, Elizabeta
AU - Trombini, Paola
AU - Bozzini, Claudia
AU - Poggiali, Erika
AU - Phung, Yen
AU - Ganz, Tomas
AU - Camaschella, Clara
PY - 2007/12/1
Y1 - 2007/12/1
N2 - Inadequate hepcidin synthesis leads to iron overload in HFE-related hemochromatosis. We explored the regulation of hepcidin by iron in 88 hemochromatosis patients (61 C282Y/C282Y, 27 C282Y/H63D) and 23 healthy controls by analyzing urinary hepcidin before and 24 hours after a 65-mg oral iron dose. Thirty-four patients were studied at diagnosis and had iron overload, and 54 patients were iron depleted. At diagnosis, hepcidin values in C282Y homozygotes were similar to controls, whereas values in C282Y/H63D heterozygotes were higher (P = .02). However, the hepcidin/ferritin ratio was decreased in both homozygotes (P <.001) and heterozygotes (P = .017), confirming the inadequate hepcidin production for the iron load with both genotypes. In iron-depleted patients of both genotypes studied at a time remote from phlebotomy, basal hepcidin was still lower than in controls (P <.001 for C282Y/C282Y and P = .002 for heterozygotes). After an iron challenge, meanurinary hepcidin excretion increased in controls (P = .001) but not patients, irrespective of genotype and iron status. Significant hepcidin increase ( ≥ 10 ng/mg creatinine) was observed in 74%of controls,15% of homozygotes, and 32% of heterozygotes. The hepcidin response to oral iron is blunted in HFE-related hemochromatosis and not improved after iron depletion. The findings support the involvement of HFE in iron sensing and subsequent regulation of hepcidin.
AB - Inadequate hepcidin synthesis leads to iron overload in HFE-related hemochromatosis. We explored the regulation of hepcidin by iron in 88 hemochromatosis patients (61 C282Y/C282Y, 27 C282Y/H63D) and 23 healthy controls by analyzing urinary hepcidin before and 24 hours after a 65-mg oral iron dose. Thirty-four patients were studied at diagnosis and had iron overload, and 54 patients were iron depleted. At diagnosis, hepcidin values in C282Y homozygotes were similar to controls, whereas values in C282Y/H63D heterozygotes were higher (P = .02). However, the hepcidin/ferritin ratio was decreased in both homozygotes (P <.001) and heterozygotes (P = .017), confirming the inadequate hepcidin production for the iron load with both genotypes. In iron-depleted patients of both genotypes studied at a time remote from phlebotomy, basal hepcidin was still lower than in controls (P <.001 for C282Y/C282Y and P = .002 for heterozygotes). After an iron challenge, meanurinary hepcidin excretion increased in controls (P = .001) but not patients, irrespective of genotype and iron status. Significant hepcidin increase ( ≥ 10 ng/mg creatinine) was observed in 74%of controls,15% of homozygotes, and 32% of heterozygotes. The hepcidin response to oral iron is blunted in HFE-related hemochromatosis and not improved after iron depletion. The findings support the involvement of HFE in iron sensing and subsequent regulation of hepcidin.
UR - http://www.scopus.com/inward/record.url?scp=37049024131&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=37049024131&partnerID=8YFLogxK
U2 - 10.1182/blood-2007-06-096503
DO - 10.1182/blood-2007-06-096503
M3 - Article
C2 - 17724144
AN - SCOPUS:37049024131
VL - 110
SP - 4096
EP - 4100
JO - Blood
JF - Blood
SN - 0006-4971
IS - 12
ER -