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CC chemokine receptor 5 Δ32 polymorphism in two independent cohorts of hepatitis C virus infected patients without hemophilia

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Abstract

Recently CC chemokine receptor 5 (CCR5) related immune mechanisms and a functional mutation of the CCR5 gene have been implicated in hepatitis C virus (HCV) infection in a cohort of predominantly hemophiliac patients. The present study investigated the frequency and clinical consequences of the CCR5 Δ32 mutation in two genetically homogeneous populations of HCV infected patients with a different risk profile for infection. Genomic DNA samples from 333 German patients with chronic HCV infection were screened by PCR for the presence of the CCR5 Δ32 polymorphism. In-hospital patients admitted for other diseases than viral hepatitis but with a comparable risk for HCV exposure were used as control population (n=125). Allele frequencies of CCR5 Δ32 polymorphism did not differ significantly between the two groups (7.6% and 9.5%, respectively) and control subjects (10.4%), and did not deviate from Hardy-Weinberg equilibrium in any group. Furthermore, there were no major differences between patients with respect to HCV genotypes, viral loads, liver enzymes, or fibrosis scores in relation to the presence or absence of the heterozygous CCR5 Δ32 mutation. Differences in inflammatory scores in liver biopsy samples and response to antiviral therapy in CCR5 Δ32 heterozygotes in one cohort could neither be reproduced in the other group of patients nor when both cohorts were pooled. These results argue against a strong effect of the CCR5 Δ32 deletion regarding these phenotypes. In conclusion, we found no increased frequency of the CCR5 Δ32 polymorphism in two independent cohorts of patients with HCV infection but without hemophilia as the main risk factor for infection. As the major difference to investigations demonstrating an association between CCR5 Δ32 and HCV infection is the selection of cases and controls, our study emphasizes the importance of epidemiological criteria for association studies of HCV infection.

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Abbreviations

CCR :

CC chemokine receptor

HCV :

Hepatitis C virus

HIV :

Human immunodeficiency virus

HWE :

Hardy-Weinberg equilibrium

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Acknowledgements

This work was supported by grants from the Federal Ministry of Education and Research (BMBF Network of Competence in Medicine, Hep-Net), the Ministry of Science and Research (MWF) of North-Rhine–Westphalia, and Aachen University (START grants). The authors thank Hildegard Keppeler (Aachen) for excellent technical assistance.

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Authors and Affiliations

  1. Department of Medicine III, University Hospital Aachen, Aachen University (RWTH), Pauwelsstrasse 30, 52074, Aachen, Germany

    Hermann E. Wasmuth, Alexa Werth, Christoph G. Dietrich, Andreas Geier, Ramin Schirin-Sokhan, Carsten Gartung, Siegfried Matern & Frank Lammert

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

    Tobias Mueller & Thomas Berg

  3. Institute of Pathology, University Hospital Aachen, Aachen University (RWTH), Pauwelsstrasse 30, 52074, Aachen, Germany

    Johann Lorenzen

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  1. Hermann E. Wasmuth
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  2. Alexa Werth
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Correspondence to Hermann E. Wasmuth.

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Wasmuth, H.E., Werth, A., Mueller, T. et al. CC chemokine receptor 5 Δ32 polymorphism in two independent cohorts of hepatitis C virus infected patients without hemophilia. J Mol Med 82, 64–69 (2004). https://doi.org/10.1007/s00109-003-0505-0

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  • DOI: https://doi.org/10.1007/s00109-003-0505-0

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