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Published on: February 19, 2019
Analysis of polymorphism and hepatic expression of duodenal cytochrome b in chronic hepatitis C
Alina Rudnicka1, Anna Woziwodzka1, Anna Wróblewska1
1Department of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk-Medical University of Gdansk, Gdansk, Poland.
Insights
The duodenal cytochrome b gene (CYBRD1) variant rs884409 is linked to increased iron overload, inflammation, and oxidative stress in chronic hepatitis C patients. This implicates CYBRD1 in the disease
Area of Science:
- Hepatology
- Genetics
- Molecular Biology
Background:
- Pathological iron overload is a common negative prognostic factor in chronic hepatitis C (CHC).
- A single nucleotide polymorphism (SNP) rs884409 in the duodenal cytochrome b gene (CYBRD1) is associated with hemochromatosis.
- The role of CYBRD1 in iron overload within CHC patients requires further investigation.
Purpose of the Study:
- To investigate the impact of CYBRD1 genotype and expression on iron overload in CHC patients.
- To analyze the association between SNP rs884409 and iron homeostasis markers.
- To examine the correlation between CYBRD1 expression and iron-related gene regulators.
Main Methods:
- Analysis of liver biopsy and whole blood samples from 243 CHC patients.
- Assessment of hepatic iron deposits, serum iron markers, and iron homeostasis gene expression.
- Genotyping for CYBRD1 SNP rs884409 and quantitative gene expression analysis.
Main Results:
- The rs884409 G allele correlated with elevated serum iron, liver inflammation, and oxidative stress.
- Hepatic CYBRD1 expression was linked to Tfr2, Id1, and HO-1 gene expression.
- Increased CYBRD1 expression was associated with higher serum ferritin and hepatic iron accumulation.
Conclusions:
- CYBRD1 plays a significant role in iron homeostasis in the context of chronic hepatitis C.
- The CYBRD1 SNP rs884409 may serve as a genetic marker for iron overload in CHC.
- CYBRD1 expression levels are indicative of iron accumulation and associatedpathological processes in CHC.
Background And Aim:
Pathological iron overload is commonly found in chronic hepatitis C (CHC) patients and considered as a negative prognostic factor of the disease. A single nucleotide polymorphism (SNP) rs884409 in duodenal cytochrome b gene (CYBRD1) is implicated in the pathogenesis of hemochromatosis. In our study we investigated the impact of the CYBRD1 genotype and expression on iron overload in CHC patients.
Methods:
Liver biopsy specimens and whole blood samples from 243 patients with CHC were included in the study. Iron deposits in hepatocytes, serum markers of iron overload, and expression profile of gene-regulators of iron homeostasis were analyzed. Genotyping and analysis of gene expression of the CYBRD1 were performed. The frequency of SNP and the expression levels of CYBRD1 were compared between the groups of patients with and without markers of iron overload.
Results:
The single nucleotide variant rs884409 G was associated with elevated serum iron levels, increased markers of liver inflammation, and oxidative stress. Hepatic expression of CYBRD1 was associated with the expression of Tfr2, Id1, and HO-1 genes, serum ferritin levels, and with increased iron accumulation in liver.
Conclusion:
These results implicate CYBRD1 involvement in iron homeostasis in CHC.
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