Patients with alcoholic liver disease (ALD) often display disturbed iron indices. Hepcidin, a key regulator of iron metabolism, has been shown to be down-regulated by alcohol in cell lines and animal models. This down-regulation led to increased duodenal iron transport and absorption in animals. In this study, we investigated gene expression of duodenal iron transport molecules and hepcidin in three groups of patients with ALD (with anaemia, with iron overload and without iron overload) and controls. Expression of DMT1, FPN1, DCYTB, HEPH, HFE and TFR1 was measured in duodenal biopsies by using real-time PCR and Western blot. Serum hepcidin levels were measured by using ELISA. Serum hepcidin was decreased in patients with ALD. At the mRNA level, expressions of DMT1, FPN1 and TFR1 genes were significantly increased in ALD. This pattern was even more pronounced in the subgroups of patients without iron overload and with anaemia. Protein expression of FPN1 paralleled the increase at the mRNA level in the group of patients with ALD. Serum ferritin was negatively correlated with DMT1 mRNA. The down-regulation of hepcidin expression leading to up-regulation of iron transporters expression in the duodenum seems to explain iron metabolism disturbances in ALD. Alcohol consumption very probably causes suppression of hepcidin expression in patients with ALD.

• Klíčová slova
• DCYTB, DMT1, FPN1, HEPH, HFE, TFR1, alcoholic liver disease, gene expression, hepcidin, iron,
• MeSH
• alkoholické nemoci jater metabolismus   MeSH
• cytochromy typu b genetika   metabolismus   MeSH
• dospělí MeSH
• duodenum metabolismus   MeSH
• exprese genu MeSH
• ferroportin MeSH
• hepcidiny fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové proteiny genetika   metabolismus   MeSH
• oxidoreduktasy genetika   metabolismus   MeSH
• proteiny přenášející kationty genetika   metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• železo krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CYBRD1 protein, human MeSH Prohlížeč
• cytochromy typu b MeSH
• ferroportin MeSH
• hepcidiny MeSH
• HEPH protein, human MeSH Prohlížeč
• membránové proteiny MeSH
• oxidoreduktasy MeSH
• proteiny přenášející kationty MeSH
• solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2 MeSH Prohlížeč
• železo MeSH

Disturbances of iron metabolism are observed in chronic liver diseases. In the present study, we examined gene expression of duodenal iron transport molecules and hepcidin in patients with hereditary hemochromatosis (HHC) (treated and untreated), involving various genotypes (genotypes which represent risk for HHC were examined), and in patients with iron deficiency anaemia (IDA). Gene expressions of DMT1, ferroportin, Dcytb, hephaestin, HFE and TFR1 were measured in duodenal biopsies using real-time PCR and Western blot. Serum hepcidin levels were measured using ELISA. DMT1, ferroportin and TFR1 mRNA levels were significantly increased in post-phlebotomized hemochromatics relative to controls. mRNAs of all tested molecules were significantly increased in patients with IDA compared to controls. The protein expression of ferroportin was increased in both groups of patients but not significantly. Spearman rank correlations showed that DMT1 versus ferroportin, Dcytb versus hephaestin and DMT1 versus TFR1 mRNAs were positively correlated regardless of the underlying cause, similarly to protein levels of ferroportin versus Dcytb and ferroportin versus hephaestin. Serum ferritin was negatively correlated with DMT1 mRNA in investigated groups of patients, except for HHC group. A decrease of serum hepcidin was observed in IDA patients, but this was not statistically significant. Our data showed that although untreated HHC patients do not have increased mRNA levels of iron transport molecules when compared to normal subjects, the expression is relatively increased in relation to body iron stores. On the other hand, post-phlebotomized HHC patients had increased DMT1 and ferroportin mRNA levels possibly due to stimulated erythropoiesis after phlebotomy.

• MeSH
• biologický transport MeSH
• deficit železa * MeSH
• dospělí MeSH
• duodenum metabolismus   MeSH
• fenotyp MeSH
• hemochromatóza krev   genetika   metabolismus   MeSH
• hepcidiny MeSH
• kationické antimikrobiální peptidy krev   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• proteiny přenášející kationty genetika   metabolismus   MeSH
• regulace genové exprese MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• železo metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• HAMP protein, human MeSH Prohlížeč
• hepcidiny MeSH
• kationické antimikrobiální peptidy MeSH
• messenger RNA MeSH
• proteiny přenášející kationty MeSH
• železo MeSH