Abstract
BackgroundCytokines 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.FindingsPatients 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-γ (+874 T/A), TNF-α (−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-γ (+874 T/A), TNF-α (−238 G/A and −308 G/A) polymorphisms did not show significant association with spontaneous viral clearance or chronicity.ConclusionThe 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.
Highlights
ObjectivesThe aim of this study was to investigate whether Single nucleotide polymorphism (SNP) in genes involved in humoral and cellular immune responses as well as in genes associated with activation of the antiviral state influence the outcome of the disease towards spontaneous viral clearance or chronicity
Cytokines play an important role in the regulation of the immune response
The individual susceptibility and the outcome of hepatitis C virus (HCV) infection have been associated to polymorphisms of cytokines genes [2,3,4,5], and pathogenesis is related to the genotype of the virus as well as the immune response of the host [6,7]
Summary
The aim of this study was to investigate whether SNPs in genes involved in humoral and cellular immune responses as well as in genes associated with activation of the antiviral state influence the outcome of the disease towards spontaneous viral clearance or chronicity. This study aims to evaluate the genotype and allele frequencies of IL-10 C-592A, C-819 T and A-1082 G, IL-4 C + 33 T, IFN-γ T + 874A, and TNF-α G-238A, G-308A, a group of cytokines representative of TH1 and TH2 response, respectively, and IL28B Crs12979860T, Trs8099917G a cytokine associated with the induction of antiviral state in the cell and its association with the outcome of HCV infection in a group of Brazilian patients
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