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

Background Although the gene for hereditary haemochromatosis has been clone d, the mechanism by which iron uptake is inappropriately increased in this disorder is unclear. Iron absorption is regulated by the duodenal metal tra nsporter, DMT-1, also called NRAMP-2. We investigated the expression of NRA MP-2 in patients with hereditary haemochromatosis. Methods Duodenal biopsy samples were taken from 20 patients with haemochrom atosis homozygous for the C282Y mutation and from ten controls. NRAMP-2 exp ression 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 signif icantly higher NRAMP-2 cDNA concentrations in patients than in controls (me an 3.43 [SD 0.61] vs 1.11 [0.74] log ng competitorx10(4); p<0.001). No muta tions 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 i n patients (r=-0.18, p=0.8). Interpretation Increased NRAMP-2 mRNA expression in duodenal mucosa of pati ents with hereditary haemochromatosis may promote duodenal iron uptake and lead to iron overload.