Bi-allelic presence of the interleukin-10 receptor 1 G330R allele is associated with cirrhosis in chronic HCV-1 infection
| Autor: | Fritz Wrba, J B Neufeld, Alfred Gangl, Peter Ferenci, C. Oesterreicher, Harald Hofer, P Grundtner, Christoph Gasche |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Liver Cirrhosis Cirrhosis Hepacivirus Hepatitis C virus Immunology medicine.disease_cause Antiviral Agents chemistry.chemical_compound Interferon Ribavirin Genetics medicine Humans Genetic Predisposition to Disease Receptors Interleukin-10 Allele frequency Genetics (clinical) Aged biology Hepatitis C Receptors Interleukin Middle Aged biology.organism_classification medicine.disease chemistry Amino Acid Substitution Interferons Hepatic fibrosis medicine.drug |
| Zdroj: | Genes and immunity. 6(3) |
| ISSN: | 1466-4879 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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