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Hemochromatosis and transferrin receptor gene polymorphisms in chronic hepatitis C: impact on iron status, liver injury and HCV genotype

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Abstract

Mild iron overload in chronic hepatitis C is associated with liver fibrosis, hepatitis C virus (HCV) genotype 1b infection, and an impaired response to interferon therapy. In this study we evaluated whether polymorphisms in the hemochromatosis gene HFE and the transferrin receptor gene TFR1 are associated with these typical findings. The study considered 246 HCV-infected patients and 200 blood donors as controls, in which C282Y, H63D, and S65C mutations (HFE) and the S142G polymorphism (TFR1) were detected. HCV genotype, serum ferritin levels, stainable intrahepatic iron, and grade of fibrosis according to the METAVIR score (F0–F4) were determined. In HCV-infected patients, heterozygosity for the C282Y mutation in HFE was significantly associated with elevated serum ferritin levels, stainable liver iron, and advanced fibrosis or cirrhosis (F2–F4). By multivariate logistic regression analysis the odds ratio for the development of advanced fibrosis or cirrhosis (F2–F4) was 2.5 for HCV-infected patients carrying a heterozygous C282Y mutation and 4.8 for HCV-infected patients with C282Y/H63D and C282Y/S65C compound heterozygosity. Heterozygosity for the C282Y mutation in HFE contributes to iron accumulation and fibrosis progression in chronic hepatitis C.

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Abbreviations

HCV :

Hepatitis C virus

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Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (grant STR 216/10-1) and by the Forschungsförderungsprogramm of the College of Medicine, University of Heidelberg, Germany.

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Authors and Affiliations

  1. Department of Internal Medicine IV, University Hospital of Heidelberg, Bergheimer Strasse 58, 69115, Heidelberg, Germany

    Sven G. Gehrke, Wolfgang Stremmel, Inge Mathes, Hans-Dieter Riedel, Karin Bents & Birgit Kallinowski

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  1. Sven G. Gehrke
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  2. Wolfgang Stremmel
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  3. Inge Mathes
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  4. Hans-Dieter Riedel
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Correspondence to Wolfgang Stremmel.

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Gehrke, S.G., Stremmel, W., Mathes, I. et al. Hemochromatosis and transferrin receptor gene polymorphisms in chronic hepatitis C: impact on iron status, liver injury and HCV genotype. J Mol Med 81, 780–787 (2003). https://doi.org/10.1007/s00109-003-0493-0

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  • DOI: https://doi.org/10.1007/s00109-003-0493-0

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