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

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.
AuthorsH Hofer, J B Neufeld, C Oesterreicher, P Grundtner, F Wrba, A Gangl, P Ferenci, C Gasche
JournalGenes and immunity (Genes Immun) Vol. 6 Issue 3 Pg. 242-7 (May 2005) ISSN: 1466-4879 [Print] England
PMID15729365 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiviral Agents
  • Receptors, Interleukin
  • Receptors, Interleukin-10
  • Ribavirin
  • Interferons
Topics
  • Adult
  • Aged
  • Amino Acid Substitution
  • Antiviral Agents (pharmacology)
  • Genetic Predisposition to Disease
  • Hepacivirus (metabolism)
  • Hepatitis C (complications, drug therapy, physiopathology)
  • Humans
  • Interferons (pharmacology)
  • Liver Cirrhosis (genetics, metabolism, physiopathology, virology)
  • Middle Aged
  • Receptors, Interleukin (genetics, metabolism)
  • Receptors, Interleukin-10
  • Ribavirin (pharmacology)

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