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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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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DOI: https://doi.org/10.1038/sj.gene.6364168