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Bi-allelic presence of the interleukin-10 receptor 1 G330R allele is associated with cirrhosis in chronic HCV-1 infection

Genes & Immunity volume 6, pages 242–247 (2005)Cite this article

Abstract

Immune response to viral infection is an important determinant of liver injury in chronic hepatitis C (CHC). Experimental and clinical data suggest a protective role of interleukin-10 (IL-10) in hepatic fibrogenesis. The significance of two SNPs of the interleukin-10 receptor 1 (IL-10R1), S138G (SNP3) and G330R (SNP4) was investigated on (i) susceptibility to CHC, (ii) progression of hepatic fibrosis and (iii) response to interferon/ribavirin therapy. DNA and liver biopsies were obtained from 212 patients with HCV (hepatitis C virus)-genotype-1 infection. The allele frequencies were 0.17 for SNP3 and 0.33 for SNP4, both of which were indifferent from healthy controls (0.17 and 0.32, respectively). Stage 1 liver fibrosis was found in 22 cases (10.4%), stage 2 in 108 (50.9%), stage 3 in 27 (12.8%), and stage 4 (cirrhosis) in 55 (25.9%). An association was found between the SNP4 allele and the presence of cirrhosis (P=0.01). Homozygous SNP4 individual variants segregated within the cirrhosis group (P=0.03). We found neither an association with SNP3 nor with the necroinflammatory disease activity (as measured by ALT levels) nor with the response to antiviral therapy. Our work implies that IL-10R1 SNP4 is a recessively inherited risk factor for hepatic cirrhosis in HCV genotype-1 infection.

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Abbreviations

IL-10:

interleukin-10

IL-10R1:

interleukin-10 receptor 1

cSNP:

coding single-nucleotide polymorphism

PCR:

polymerase chain reaction

PBMC:

peripheral blood mononuclear cells

CHC:

chronic hepatitis C

HCV:

hepatitis C virus

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Acknowledgements

This work was supported by the Austrian Science Foundation P15314 and the OeNB Anniversary Fund ONB10543 to CG.

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Authors and Affiliations

  1. Department of Internal Medicine IV, Division of Gastroenterology and Hepatology, Medical University of Vienna, Austria

    H Hofer, J B Neufeld, C Oesterreicher, P Grundtner, A Gangl, P Ferenci & C Gasche

  2. Department of Clinical Pathology, Medical University of Vienna, Austria

    F Wrba

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  1. H Hofer
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  2. J B Neufeld
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Correspondence to C Gasche.

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Hofer, H., Neufeld, J., Oesterreicher, C. et al. Bi-allelic presence of the interleukin-10 receptor 1 G330R allele is associated with cirrhosis in chronic HCV-1 infection. Genes Immun 6, 242–247 (2005). https://doi.org/10.1038/sj.gene.6364168

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