Abstract
Several studies investigated associations of IFN-γ rs2430561 T/A, IL28B rs12979860 C/T and ERα rs2077647 T/C gene polymorphisms with outcomes of hepatitis B virus (HBV) infection, but the results were controversial. Therefore, we performed a meta-analysis of all published observational studies to address this inconsistency. Literature was searched in online database and a systematic review was conducted based on the search results. A total of 24 studies were included and dichotomous data were presented as odds ratio (OR) with a 95% confidence interval (CI). The rs2430561 T allele was associated with reduced persistent HBV infection risk (T vs. A: OR, 0.690; 95% CI, [0.490, 0.971]), while the rs2077647 T allele significantly increased the risk of persistent HBV infection (T vs. C: OR, 1.678; 95% CI, [1.212, 2.323]). Rs 2077647 CC might play a role in protecting individuals against HBV persistence (TT vs. CC: OR, 4.109; 95% CI, [2.609, 6.473]). Furthermore, carriers of the rs2430561 TT genotype were more likely to clear HBV spontaneously compared with those of the AA genotype (TT vs. AA: OR, 0.555; 95% CI, [0.359, 0.856]). For rs12979860 C/T polymorphism, no significant correlation with HBV infection outcomes was found. In subgroup analyses, the results were similar to those of overall analysis. However, for rs2077647 TT vs. TC+CC, significantly increased risks were observed in the Asian and hospital-based population, but not in the overall analysis. IFN-γ rs2430561 T/A and ERα rs2077647 T/C genetic polymorphisms were associated with outcomes of HBV infection, but no association was found between IL28B rs12979860 C/T and HBV infection.
Highlights
Infection by hepatitis B virus (HBV) appears under different forms of evolution, ranging from the asymptomatic and self-limited infection to the chronic state, which can develop into chronic hepatitis, cirrhosis, and hepatocellular carcinoma[1]
Association of individual polymorphisms with susceptibility to persistent HBV infection We compared persistent HBV infection cases with healthy controls to discover the relation of IFN-c rs2430561 T/A, IL28B rs12979860 C/T and ERa rs2077647 T/C single nucleotide polymorphism (SNP) to persistent HBV infection susceptibility
No evidence of a relationship between IL28B rs12979860 C/T and persistent HBV infection risk was observed in all comparison models
Summary
Infection by hepatitis B virus (HBV) appears under different forms of evolution, ranging from the asymptomatic and self-limited infection to the chronic state, which can develop into chronic hepatitis, cirrhosis, and hepatocellular carcinoma[1]. Factors that determine the variable outcomes of HBV infection are little known. Environment factors, ethnic differences and genetic susceptibility have been reported to have an effect on the progression of this liver disease[2]. A number of studies have shown that genetic polymorphisms of cytokines have a correlation with the outcomes of HBV infection[3,4]. A single nucleotide polymorphism (SNP) located in the IFN-c gene intron (at position +874) was involved in transcriptional regulation of IFN-c [7] and HBV susceptibility[8]. Some studies demonstrated that patients carrying rs2430561 AA genotype in the IFN-c gene had a high risk of susceptibility to chronic infection of HBV[9,10,11], while Cheong et al.[12] observed no significant difference in susceptibility risk
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