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Association of MRC-1 and IL-28B with the treatment outcome of hepatitis C: a case control study.

ABSTRACT: BACKGROUND:The aim of this study was to evaluate whether polymorphisms of the mannose receptor C type 1 (MRC-1) and interleukin 28B (IL-28B) genes are associated with the treatment outcome of patients infected with hepatitis C virus genotypes 1 and 2 (HCV-1 and HCV-2, respectively) who are treated with peginterferon plus ribavirin (PEG-IFN?-RBV). METHODS:We analyzed the association of the patients' sustained viral responses (SVRs) to PEG-IFN?-RBV therapy with 2 single nucleotide polymorphisms (SNPs) in MRC-1 and 3 SNPs in IL-28B. We selected patients infected with either HCV-1 (n = 265) or HCV-2 (n = 195) with or without SVR. RESULTS:Among the MRC-1 SNPs, rs691005 was found to be associated with SVR in HCV-1-infected patients (P < 0.0001). The IL-28B rs8099917 SNP was found to be associated with SVR in HCV-1- and HCV-2-infected patients (HCV-1, P < 0.0001; HCV-2, P = 0.002), while IL-28B rs955155 and rs10853728 SNPs were found to be associated with SVR in HCV-1-infected patients (P = 0.003) and HCV-2-infected patients (P = 0.02), respectively. We also identified an interaction between MRC-1 rs691005 and IL-28B rs8099917 (P = 0.001). The C-T haplotype was shown to have a positive effect on SVR in HCV-1-infected patients (OR = 1.77, 95% CI = 1.2, 2.62), whereas the T-G haplotype was shown to have a negative effect on SVR in HCV-1-infected patients (OR = 0.28, 95% CI = 0.14, 0.58). CONCLUSIONS:These results suggest that SNPs of IL-28B and MRC-1 can be used as genetic markers for predicting the outcome of PEG-IFN?-RBV treatment of HCV infections.

SUBMITTER: Peng CY

PROVIDER: S-EPMC4098956 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Association of MRC-1 and IL-28B with the treatment outcome of hepatitis C: a case control study.

Peng Cheng-Yuan CY Chen Ter-Hsin TH Lim Yun-Ping YP Tsai Fuu-Jen FJ Lin Wei-Yong WY Liao Wen-Ling WL Wan Lei L

BMC gastroenterology 20140626

<h4>Background</h4>The aim of this study was to evaluate whether polymorphisms of the mannose receptor C type 1 (MRC-1) and interleukin 28B (IL-28B) genes are associated with the treatment outcome of patients infected with hepatitis C virus genotypes 1 and 2 (HCV-1 and HCV-2, respectively) who are treated with peginterferon plus ribavirin (PEG-IFNα-RBV).<h4>Methods</h4>We analyzed the association of the patients' sustained viral responses (SVRs) to PEG-IFNα-RBV therapy with 2 single nucleotide p ...[more]

PMID: 24969847

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Project description:BACKGROUND:Cytokines play an important role in the regulation of the immune response. In hepatitis C virus (HCV) infection, cytokine levels may influence the outcome of acute HCV infection. Polymorphisms in cytokine genes have been associated to different expression levels in response to infection. This study was carried out to investigate the association of several cytokine gene polymorphisms with disease outcome in HCV-infected patients. FINDINGS:Patients with chronic or spontaneously resolved HCV infection were included in a cross-sectional study. A comparative analysis was performed between the groups regarding frequency distribution of the following cytokines' gene polymorphisms: IL-10 (-1082 A/G; -819?T/C; -592 A/C), IL-4 (+33C/T), IFN-? (+874?T/A), TNF-? (-238?G/A and -308?G/A) and IL-28B (rs12979860 C/T and rs8099917 T/G). RESULTS:Eighteen patients with spontaneous viral clearance and 161 with chronic HCV infection were included. In the comparative analysis, the GG genotype of the IL-10 polymorphism -1082A/G was more frequent in patients with spontaneous viral clearance when compared to patients with chronic HCV (41.2% vs 6.2%; p = 0.001). This association was also found for the CC genotype of the IL-4 polymorphism +33C/T (72.2% vs 36.7%; p = 0.017) and the CC and TT genotypes of the IL-28B polymorphisms rs 12979860 and rs 8099917 (88.9% vs 30.3%; p?<?0.001 and 88.9% vs 49.6%; p = 0.002). The IL10 (A-1082?G) and IL-28B (Crs12979860T) gene polymorphisms showed odds ratios of 12.848 and 11.077, respectively, and thus may have a greater influence on HCV spontaneous viral clearance. The IFN-? (+874?T/A), TNF-? (-238?G/A and -308?G/A) polymorphisms did not show significant association with spontaneous viral clearance or chronicity. CONCLUSION:The G allele for IL-10 (-1082 A/G), the C allele for IL-4 (+3 C/T) and the C and T alleles for IL-28B (rs12979860 and rs8099917, respectively) are associated with spontaneous viral clearance in hepatitis C infection.

Dataset Information

Association of MRC-1 and IL-28B with the treatment outcome of hepatitis C: a case control study.

Publications

Association of MRC-1 and IL-28B with the treatment outcome of hepatitis C: a case control study.

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