BACKGROUND: Coronavirus disease (COVID-19), which is caused by the SARS-CoV-2 virus, has become a global pandemic. While susceptibility to COVID-19 is subject to several external factors, including hypertension, BMI, and the presence of diabetes, it is also genetically determined to a significant extent. Infectious agents require iron (Fe) for proper functioning. Carriers of mutations resulting in increased iron concentrations are understood to be at increased risk of COVID-19. METHODS: We examined HFE genotypes associated with hereditary haemochromatosis (rs1800562 and rs1799945 SNPs) in 617 COVID-19 patients (166 asymptomatic, 246 symptomatic and 205 hospitalised survivors) and 2 559 population-based controls. RESULTS: We found a higher frequency of the minor allele (Tyr282) of the rs1800562 polymorphism (P < 0.002) in patients compared to controls (8.5 % vs 5.5 %). Non-carriers of the minor allele were protected against SARS-Cov-2 infection (OR, 95 %CI; 0.59, 0.42-0.82). The frequency of minor allele carriers was almost identical across asymptomatic, symptomatic, and hospitalised survivors. The rs1799945 variant did not affect disease severity and its occurrence was almost identical in patients and controls (P between 0.58 and 0.84). CONCLUSIONS: In conclusion, our results indicate that presence of the rs1800562 minor allele, which is associated with hereditary haemochromatosis (thus increased levels of plasma Fe), increases susceptibility to SARS-CoV-2.

• Keywords
• COVID-19, HFE, Iron, Polymorphism, Susceptibility,
• MeSH
• COVID-19 * genetics   MeSH
• Hemochromatosis * genetics   epidemiology   MeSH
• Polymorphism, Single Nucleotide MeSH
• Humans MeSH
• Histocompatibility Antigens Class I genetics   MeSH
• Mutation MeSH
• Hemochromatosis Protein genetics   MeSH
• SARS-CoV-2 MeSH
• Iron MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• HFE protein, human MeSH Browser
• Histocompatibility Antigens Class I MeSH
• Hemochromatosis Protein MeSH
• Iron MeSH

Duodenal biopsies are considered a suitable source of enterocytes for studies of dietary iron absorption. However, the expression level of molecules involved in iron absorption may vary along the length of duodenum. We aimed to determine whether the expression of molecules involved in the absorption of heme and non-heme iron differs depending on the location in the duodenum. Analysis was performed with samples of duodenal biopsies from 10 individuals with normal iron metabolism. Samples were collected at the following locations: (a) immediately post-bulbar, (b) 1-2 cm below the papilla of Vater and (c) in the distal duodenum. The gene expression was analyzed at the mRNA and protein level using real-time PCR and Western blot analysis. At the mRNA level, significantly different expression of HCP1, DMT1, ferroportin and Zip8 was found at individual positions of duodenum. Position-dependent expression of other molecules, especially of FLVCR1, HMOX1 and HMOX2 was also detected but with no statistical significances. At the protein level, we observed statistically significantly decreasing expression of transporters HCP1, FLVCR1, DMT1, ferroportin, Zip14 and Zip8 with advancing positions of duodenum. Our results are consistent with a gradient of diminishing iron absorption along the duodenum for both heme and non-heme iron.

• Keywords
• heme iron absorption, iron transport, iron uptake in duodenum, non-heme iron absorption,
• MeSH
• Duodenum * metabolism   MeSH
• Heme metabolism   MeSH
• Ion Transport MeSH
• Humans MeSH
• RNA, Messenger genetics   metabolism   MeSH
• Iron * metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Heme MeSH
• RNA, Messenger MeSH
• Iron * MeSH

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.

• Keywords
• DCYTB, DMT1, FPN1, HEPH, HFE, TFR1, alcoholic liver disease, gene expression, hepcidin, iron,
• MeSH
• Liver Diseases, Alcoholic metabolism   MeSH
• Cytochrome b Group genetics   metabolism   MeSH
• Adult MeSH
• Duodenum metabolism   MeSH
• Gene Expression MeSH
• Ferroportin MeSH
• Hepcidins physiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Membrane Proteins genetics   metabolism   MeSH
• Oxidoreductases genetics   metabolism   MeSH
• Cation Transport Proteins genetics   metabolism   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Iron blood   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• CYBRD1 protein, human MeSH Browser
• Cytochrome b Group MeSH
• Ferroportin MeSH
• Hepcidins MeSH
• HEPH protein, human MeSH Browser
• Membrane Proteins MeSH
• Oxidoreductases MeSH
• Cation Transport Proteins MeSH
• solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2 MeSH Browser
• Iron 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
• Biological Transport MeSH
• Iron Deficiencies * MeSH
• Adult MeSH
• Duodenum metabolism   MeSH
• Phenotype MeSH
• Hemochromatosis blood   genetics   metabolism   MeSH
• Hepcidins MeSH
• Antimicrobial Cationic Peptides blood   metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• RNA, Messenger genetics   metabolism   MeSH
• Cation Transport Proteins genetics   metabolism   MeSH
• Gene Expression Regulation MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Iron metabolism   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• HAMP protein, human MeSH Browser
• Hepcidins MeSH
• Antimicrobial Cationic Peptides MeSH
• RNA, Messenger MeSH
• Cation Transport Proteins MeSH
• Iron MeSH