HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Nelson, J. E. Articles by Kowdley, K. V PubMed PubMed Citation Articles by Nelson, J. E. Articles by Kowdley, K. V

Research Article

RELATIONSHIP BETWEEN GENE EXPRESSION OF DUODENAL IRON TRANSPORTERS AND IRON STORES IN HEMOCHROMATOSIS SUBJECTS

¹Virginia Mason Medical Center ^{2 3}university of Washington

Submitted 8 May 2009 ; revision received 20 October 2009 ; accepted in final form 3 November 2009

ABSTRACT

To test the hypothesis that differences in duodenal iron absorption may explain the variable phenotypic expression among HFE C282Y homozygotes, we have compared relative gene expression of duodenal iron transporters among C282Y homozygotes (HH) with and without iron overload. Duodenal biopsy samples were analyzed using real time PCR for expression of DMT1, FPN1, DCYTB and HEPH relative to GAPDH from 23 C282Y homozygotes, including 5 "non-expressors" (serum ferritin<ULN and absence of phenotypic features of hemochromatosis) and 18 "expressors". Four subjects wild type for HFE mutations without iron overload or liver disease served as controls. There was a significant difference in expression of DMT1 (p= 0.03) and DMT(IRE) (p=0.0013) but not FPN1, DCYTB or HEPH between groups. Expression of DMT1(IRE) was increased among HH subjects after phlebotomy compared to untreated (p=0.006) and non-expressor groups (p=0.026). A positive relationship was observed among all HH subjects regardless of phenotype or treatment status between relative expression of FPN and DMT1 (r=0.5854, p=0.0021), FPN1 and DCYTB (r=0.5554, p=0.0040), FPN1 and HEPH (r=0.5100, p=0.0092) and DCYTB and HEPH (r=0.5400, p=0.0053). In summary, phlebotomy is associated with upregulation of DMT1 (IRE) expression in HH subjects. HFE C282Y homozygotes without phenotypic expression do not have significantly decreased duodenal gene expression of iron transport genes compared to HH subjects with iron overload. There is coordinated regulation between duodenal expression of FPN and DMT1, FPN and DCYTB and FPN and HEPH and also DCYTB and HEPH in HH subjects regardless of phenotype.

hemochromatosis; duodenum iron transporters; DMT1, FPN1; iron metabolism