Viral Hepatitis

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Haplotype-tagging RANTES gene variants influence response to antiviral therapy in chronic hepatitis C†

  1. Hermann E. Wasmuth1,
  2. Alexa Werth1,
  3. Tobias Mueller3,
  4. Thomas Berg3,
  5. Christoph G. Dietrich1,
  6. Andreas Geier1,
  7. Carsten Gartung1,
  8. Johann Lorenzen2,
  9. Siegfried Matern1,
  10. Frank Lammert1,‡,*

Article first published online: 13 AUG 2004

DOI: 10.1002/hep.20322

Issue

Hepatology

Hepatology

Volume 40, Issue 2, pages 327–334, August 2004

Additional Information

How to Cite

Wasmuth, H. E., Werth, A., Mueller, T., Berg, T., Dietrich, C. G., Geier, A., Gartung, C., Lorenzen, J., Matern, S. and Lammert, F. (2004), Haplotype-tagging RANTES gene variants influence response to antiviral therapy in chronic hepatitis C. Hepatology, 40: 327–334. doi: 10.1002/hep.20322

Author Information

  1. 1

    Department of Medicine III, University Hospital Aachen, Aachen University, Aachen, Germany

  2. 2

    Institute of Pathology, University Hospital Aachen, Aachen University, Aachen, Germany

  3. 3

    Department of Hepatology and Gastroenterology, University Hospital Charité, Humboldt University, Berlin, Germany

  1. ‡

    fax: +49 241 80-82455

*Department of Medicine III, University Hospital Aachen (UKA), Aachen University (RWTH), Pauwelsstrasse 30, 52057 Aachen, Germany

  1. †

    This paper was presented, in part, at the Annual Meeting of the German Gastroenterological Association, Nürnberg, September 2003, and the Hepatitis C Therapy Session of the Annual Meeting of the American Association for the Study of Liver Diseases, Boston, October 2003, and was published in abstract form in Z Gastroenterol 2003;41:798–799 and HEPATOLOGY 2003;38:245A.

  2. ‡

    fax: +49 241 80-82455

Publication History

  1. Issue published online: 13 AUG 2004
  2. Article first published online: 13 AUG 2004
  3. Manuscript Accepted: 29 APR 2004
  4. Manuscript Received: 5 JAN 2004

Funded by

  • Federal Ministry of Education and Research (BMBF Network of Competence in Medicine Hep-Net)
  • Ministry of Science and Research (MWF) of North-Rhine-Westphalia
  • Aachen University (START grants)

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Abstract

The response to antiviral therapy for chronic hepatitis C virus (HCV) is complex and is determined by both environmental and genetic factors. Recently, interacting gene polymorphisms of the chemokine RANTES have been shown to affect HIV disease progression. Our aim was to assess if these RANTES variants are associated with response to anti-HCV therapy. Three linked RANTES single nucleotide polymorphisms (403 G/A, Int1.1 T/C, and 3′ 222 T/C) were determined in 297 Caucasian patients who were treated for chronic HCV infection and 152 control subjects. Characteristic nucleotide combinations on single chromosomes (haplotypes) were reconstructed and tested for disease association. Four common RANTES haplotypes (prevalence 73%) were identified in patients and controls. There was a strong association of RANTES haplotype distribution with outcome of antiviral combination therapy (P = .007). Specifically, RANTES haplotypes carrying Int1.1 C and 3′ 222 C alleles were more frequent in nonresponders than in patients with a sustained response to antiviral therapy (odds ratio 1.9, P = .01). The influence of these RANTES haplotypes on the outcome of therapy was more pronounced in patients infected with HCV genotypes 1 and 4 (odds ratio 2.3, P = .02). Because RANTES haplotypes carrying Int1.1 C are known to down-regulate RANTES transcriptional activity in vitro, the haplotype analysis fits the hypothesis of a diminished T helper 1 lymphocyte response in patients with a negative response to antiviral therapy. In conclusion, RANTES haplotypes might contribute to the polygenic interaction between HCV and the host immune system and could help to risk stratify patients prior to antiviral therapy. (HEPATOLOGY 2004;40:327–334.)

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