Duodenal expression of iron transport molecules in untreated haemochromatosis subjects.
OBJECTIVE
In HFE associated hereditary haemochromatosis, the duodenal enterocyte behaves as if iron deficient and previous reports have shown increased duodenal expression of divalent metal transporter 1 (DMT1) and iron regulated gene 1 (Ireg1) in affected subjects. In those studies, many patients had undergone venesection, which is a potent stimulus of iron absorption. Our study investigated duodenal expression of DMT1 (IRE and non-IRE), Ireg1, hephaestin, and duodenal cytochrome-b (Dyctb) in untreated C282Y homozygous haemochromatosis patients, iron deficient patients, and iron replete subjects.


METHODS
Total RNA was extracted from duodenal biopsies and expression of the iron transport genes was assessed by ribonuclease protection assay.


RESULTS
Expression of DMT1 (IRE) and Ireg1 was increased 3-5-fold in iron deficient subjects compared with iron replete subjects. Duodenal expression of DMT1 (IRE) and Ireg1 was similar in haemochromatosis patients and iron replete subjects but in haemochromatosis patients with elevated serum ferritin concentrations, both DMT1 (IRE) and Ireg1 expression were inappropriately increased relative to serum ferritin concentration. Hephaestin and Dcytb levels were not upregulated in haemochromatosis. DMT1 (IRE) and Ireg1 levels showed significant inverse correlations with serum ferritin concentration in each group of patients.


CONCLUSIONS
These findings are consistent with DMT1 (IRE) and Ireg1 playing primary roles in the adaptive response to iron deficiency. Untreated haemochromatosis patients showed inappropriate increases in DMT1 (IRE) and Ireg1 expression for a given level of serum ferritin concentration, although the actual level of expression of these iron transport genes was not significantly different from that of normal subjects.
Stuart
K A
KA
Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Ipswich Road, Wooloongabba, 4102 Queensland, Australia. Drkastuart@AOL.com
Anderson
G J
GJ
Frazer
D M
DM
Powell
L W
LW
McCullen
M
M
Fletcher
L M
LM
Crawford
D H G
DH
D000293:Adolescent; D000328:Adult; D000368:Aged; D001692:Biological Transport / Q000502:physiology; D027682:Cation Transport Proteins / Q000032:analysis; D003573:Cytochrome b Group / Q000032:analysis; D004386:Duodenum / Q000378:metabolism*; D005260:Female; D005293:Ferritins / Q000097:blood; D006432:Hemochromatosis / Q000378:metabolism*; D006801:Humans; D033862:Iron-Binding Proteins / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D035925:Iron-Regulatory Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D012313:RNA / Q000032:analysis; D015854:Up-Regulation / Q000502:physiology; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D003573:Cytochrome b Group; D005293:Ferritins; D033862:Iron-Binding Proteins; D035925:Iron-Regulatory Proteins; D008565:Membrane Proteins; D012313:RNA; D000099236:Solute Carrier Family 11, Member 2; C492164:HEPH protein, human