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Association of IL-10, IL-4, and IL-28B gene polymorphisms with spontaneous clearance of hepatitis C virus in a population from Rio de Janeiro

Juliene Antonio Ramos12, Rosane Silva16, Luísa Hoffmann1, Ana Lucia Araújo Ramos34, Pedro Hernan Cabello5, Turán Péter Ürményi1, Cristiane Alves Villella-Nogueira34, Lia Lewis-Ximenez5 and Edson Rondinelli146*

Author Affiliations

1 Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

2 Instituto Federal de Educação Ciência e Tecnologia do Rio de Janeiro, Rio de Janeiro, Brazil

3 Serviço de Hepatologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

4 Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

5 Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

6 Instituto Nacional para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica, Conselho Nacional de Desenvolvimento Científico e Tecnológico/MCT, Rio de Janeiro, Brazil

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BMC Research Notes 2012, 5:508  doi:10.1186/1756-0500-5-508

Published: 17 September 2012

Abstract

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-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.

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.

Keywords:
Acute hepatitis C; Chronic hepatitis C; HCV; Spontaneous viral clearance; Cytokines; Gene polymorphism