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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Duodenal metal-transporter ( DMT-1, NRAMP-2) expression in patients with hereditary haemochromatosis.

BACKGROUND: Although the gene for hereditary haemochromatosis has been cloned, the mechanism by which iron uptake is inappropriately increased in this disorder is unclear. Iron absorption is regulated by the duodenal metal transporter, DMT-1, also called NRAMP-2. We investigated the expression of NRAMP-2 in patients with hereditary haemochromatosis. METHODS: Duodenal biopsy samples were taken from 20 patients with haemochromatosis homozygous for the C282Y mutation and from ten controls. NRAMP-2 expression was assessed by northern blotting and competitive PCR. NRAMP-2 mRNA was sequenced in seven patients and two controls. FINDINGS: Duodenal NRAMP-2 mRNA concentrations were increased in patients as estimated by Northern blotting. Accordingly, competitive PCR showed significantly higher NRAMP-2 cDNA concentrations in patients than in controls (mean 3.43 [SD 0.61] vs 1.11 [0.74] log ng competitor x 10(4); p<0.001). No mutations were found within the NRAMP-2 mRNA. Duodenal NRAMP-2 mRNA expression was correlated with serum ferritin in controls (r=-0.94, p=0.001) but not in patients (r=-0.18, p=0.8). INTERPRETATION: Increased NRAMP-2 mRNA expression in duodenal mucosa of patients with hereditary haemochromatosis may promote duodenal iron uptake and lead to iron overload.[1]

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