Duodenal Dcytb and hephaestin mRNA expression are not significantly modulated by variations in body iron homeostasis.
OBJECTIVE
While the upregulation of duodenal cytochrome b (Dcytb) within duodenal enterocytes is reported in patients with iron deficiency, the expression of hephaestin (Hp) remains controversial in altered iron metabolism states, including HFE associated hereditary hemochromatosis (HH). The effect of iron depletion therapy on the expression of these molecules is unclear. This study examines the duodenal expression of these two molecules in HH patients (prior to and following phlebotomy), in patients with iron deficiency (ID) and in healthy controls.


METHODS
Using quantitative real-time polymerase chain reaction (qRT-PCR), Dcytb and Hp mRNA expression levels were measured in duodenal tissue of C282Y homozygous HH patients, in ID patients negative for the C282Y mutation with a serum ferritin concentration less than 20 mug/l, and in controls negative for C282Y and H63D mutations with normal iron indices.


RESULTS
Dcytb and Hp mRNA expression levels were not significantly different in either non-phlebotomized and phlebotomized HH patients or individuals with iron deficiency when compared with controls. There was no significant correlation between the gene expression levels and their respective serum ferritin or TS% values in any of the investigated groups. In HH patients, there was no significant association between gene expression and the degree of hepatic parenchymal siderosis identified by Perl's iron stain. Dcytb and Hp mRNA levels were significantly correlated to each other when all cohorts were analyzed together and separately.


CONCLUSIONS
These findings demonstrate that the duodenal ferroreductase Dcytb and ferroxidase Hp mRNA expression are not significantly altered by variations in iron homeostasis. The effect of phlebotomy-induced erythropoiesis did not alter either gene transcript mRNA expression.
Gleeson
F
F
Centre for Liver Disease, Mater Misericordiae University Hospital, Dublin 7, Ireland.
Ryan
E
E
Barrett
S
S
Russell
J
J
Kelleher
B
B
Crowe
J
J
D002570:Ceruloplasmin / Q000235:genetics; D015331:Cohort Studies; D003573:Cytochrome b Group / Q000235:genetics* / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism*; D038181:FMN Reductase / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006432:Hemochromatosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D000090463:Iron Deficiencies; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D003573:Cytochrome b Group; C492164:HEPH protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D007501:Iron; D002570:Ceruloplasmin; D038181:FMN Reductase; C023903:ferric citrate iron reductase