Abstract
Human innate immune plays an essential role in the spontaneous clearance of acute infection and therapy of HCV. We investigated whether the SNPs in retinoic acid-inducible gene I-like receptor family were associated with HCV spontaneous clearance and response to treatment. To evaluate the clinical value of DDX58 rs3824456, rs10813831 and rs10738889 genotypes on HCV spontaneous clearance and treatment response in Chinese Han population, we genotyped 1001 HCV persistent infectors, 599 participants with HCV natural clearance and 354 patients with PEGylated interferon-α and ribavirin (PEG IFN-α/RBV) treatment. People carrying rs10813831-G allele genotype were more liable to achieve spontaneous clearance than the carriage of the T allele (dominant model: adjusted OR 1.35, 95% CI 1.08-1.71, P = 0.008). In rs10738889, the rate of persistent infection was significantly lower in patients with the TC genotype compared to those with TT genotype (dominant model: adjusted OR 1.36, 95% CI 1.06-1.74, P = 0.015). Multivariate stepwise analysis indicated that rs10738889, age, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were independent predictors for HCV spontaneous clearance. However, there were no significant differences in the three selection SNPs between the non-SVR group and the SVR group. These results suggest the DDX58 rs10813831 and rs10738889 are associated with spontaneous clearance of HCV, which may be identified as a predictive marker in the Chinese Han population of HCV.
Highlights
Hepatitis C is a worldwide contagious disease caused by the hepatitis C virus (HCV)
We speculate that single nucleotide polymorphisms (SNPs) in RIG-I-like receptor (RLR) family can lead to different levels of immune response and result in the individual outcomes of HCV infection
399 000 people die from hepatitis C every year, mostly from cirrhosis and hepatocellular carcinoma (WHO)
Summary
Hepatitis C is a worldwide contagious disease caused by the hepatitis C virus (HCV). Globally, it is estimated that a total of 71 million people have chronic hepatitis C infection according to the World Health Organization. HCV is spread primarily by blood-to-blood contact including intravenous drug use; transfusions, poorly sterilised medical equipment and needle stick injuries in healthcare. It may be transmitted from an infected mother to her baby during labour. We speculate that single nucleotide polymorphisms (SNPs) in RLR family can lead to different levels of immune response and result in the individual outcomes of HCV infection. Through researching the relationship between DDX58 gene polymorphism and HCV immunity level, we could discover how RIG-I affects HCV infection. Our study is intended to investigate whether several variants of DDX58 gene are associated with the outcomes of HCV infection and response to treatment. We generated data from a highrisk population to systematically examine the relationship between three SNPs (DDX58 rs3824456, rs10813831 and rs10738889) and HCV clearance
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