Journal of Molecular Medicine

, Volume 81, Issue 12, pp 780–787 | Cite as

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

  • Sven G. Gehrke
  • Wolfgang Stremmel
  • Inge Mathes
  • Hans-Dieter Riedel
  • Karin Bents
  • Birgit Kallinowski
Original Article

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.

Keywords

Hepatitis C Fibrosis Siderosis Hemochromatosis Genetic polymorphisms 

Abbreviation

HCV

Hepatitis C virus

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Sven G. Gehrke
    • 1
  • Wolfgang Stremmel
    • 1
  • Inge Mathes
    • 1
  • Hans-Dieter Riedel
    • 1
  • Karin Bents
    • 1
  • Birgit Kallinowski
    • 1
  1. 1.Department of Internal Medicine IVUniversity Hospital of HeidelbergHeidelbergGermany

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