Abstracts
1999 Digestive Disease Week

# 3482 INCREASED EXPRESSION OF DUODENAL IRON TRANSPORTER (NRAMP-2) MRNA IN DUODENAL BIOPSIES OF PATIENTS WITH HEREDITARY HEMOCHROMATOSIS
Heinz M Zoller, Univ Hosp, Innsbruck Austria; Antonello Pietrangelo, Univ of Modena, Modena Italy; Wolfgang Vogel, Univ Hosp Innsbruck, Innsbruck Austria; Guenter Weiss, Univ Hosp, Innsbruck Austria

The genetic background of heriditary hemochromatosis (HH) has been elucidated by identification of two mutations in the so called HFE gene, which is coding for a newly described MHC class I protein. Although the described mutations in the HFE gene locus seem to be sensitive and specific genetic markers for HH, the mechanism leading to increased duodenal iron uptake underlying this disease remained obscure so far. In this study we investigated the mRNA expression of the metal ion transporter NRAMP2 in duodenal biopsies of patients with HH by means of competitive RT-PCR and by means of northern blotting. We studied duodenal biopsies from 10 patients, homozygous for the C282Y mutation in the HFE gene and from 10 control subjects, who underwent routine gastroscopy because of peptic ulcer disease. Duodenal NRAMP-2 mRNA levels were highly increased in all HH patients investigated while they were hardly detectable in controls. As calculated by competitive RT-PCR and a NRAMP-2/beta actin mRNA ratio mean amount of NRAMP-2 in biopsies from patients with HH was hundredfold higher as in control subjects (p<0.001). We also sequenced NRAMP-2 cDNA from 7 HH patients, where no mutations were detectable within the NRAMP-2 cDNA. Our results provide evidence for a pathophysiological model of HH, in which increased duodenal iron uptake is maintained by increased expression of NRAMP-2 and therefore increased duodenal iron uptake. Thus, pharmacological blockade of NRAMP-2 may be an efficent future approach for treatment of HH.

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