Functional Gene Polymorphisms of Interleukin-10 are Associated with Liver Disease Progression in Japanese Patients with Hepatitis C Virus Infection

Abstract

Objective The inter-individual difference in response to liver injury appears to be important in the progression of liver fibrosis. Interleukin 10 (IL-10) is an anti-inflammatory cytokine, and several functional gene polymorphisms have been found. The aim of this study was to examine the possible association of IL-10 polymorphisms with the progression of liver fibrosis in hepatitis C virus (HCV)-related chronic liver disease patients. Methods We examined the IL-10 -1087 A/G and -824 T/C gene polymorphisms in 184 Japanese patients with HCV-related chronic liver disease: 94 chronic hepatitis (CH) and 90 with liver cirrhosis (LC). Results There were no significant differences in the genotype distributions or allele frequencies of IL-10 -824 T/C and -1087 A/G between the CH and LC groups. However, among the cirrhotic patients, the lower transcriptional allele, -824 T homozygotes had significantly lower serum albumin and platelet counts, and a higher Child-Pugh score than the -824 C carriers, and the lower transcriptional allele, -1087 A homozygotes had a higher ICG-R 15 compared with -1087 G carriers. Haplotype analysis of IL-10 -1087/-824 showed no significant difference between the CH and LC groups, but the combinations of AT and AC haplotypes (AT/ AT, AT/AC and AC/AC) had a significantly higher ICG-R 15 than the GC carriers. Conclusion IL-10 lower transcriptional -824 T allele, -1087 A allele, and -1087/-824 haplotypes AT and AC are risk factors for the progression of liver fibrosis in HCV-related chronic liver disease.

Value of serum IgG4 in the diagnosis of IgG4-related disease and in differentiation from rheumatic diseases and other diseases

“…It has been pointed out that regulatory T cell expansion in peripheral blood in cases with SSc [45] and serum levels of IL-10 correlate with skin fibrosis, such as the total skin thickness score [46]. It has also been reported that elevated levels of TGF-b reflect the severity of chronic hepatitis and liver cirrhosis [47,48], and that IL-10 gene polymorphisms are associated with the progression of liver fibrosis [49] as well as SSc. Progressive fibrosis in SSc might be associated with IgG4 through these cytokines.…”

Evolving Trends in the Hepatitis C Virus Molecular Epidemiology Studies: From the Viral Sequences to the Human Genome

“…As a consequence, it was recently reported that genetic polymorphisms in the promoter region of interleukin-10 (IL-10) are possible predictors of not only the spontaneous favourable outcome of HCV infection but also of the progression of liver fibrosis [138,139].…”

Genetic Variation of Host Immune Response Genes and Their Effect on Hepatitis C Infection and Treatment Outcome

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“…Promoter polymorphisms in IL-10, which affect the level of IL-10 production, have been shown to be associated with susceptibility to liver fibrosis. In a study of Japanese chronic HCV subjects, the IL-10 -824 T allele, -1087 A allele and -1087/-824 haplotypes AT and AC were shown to be risk factors for progression of hepatic fibrosis (Ishida, Ikebuchi et al 2011). Another study investigated the combined effect of SNPs in IL-10, IL-18 and IFN-genes on 77 chronic HCV infected patients.…”