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Cytotoxic T lymphocyte associated antigen-4(CTLA-4) is an inhibitory receptor with great value in the progression of hepatitis C virus (HCV) infection related diseases. To determine the potential associations of IL-28B rs12979860 and CTLA-4 rs231775, rs3087243 and rs5742909 polymorphisms with the generation of HCV F protein, susceptibility and outcomes of HCV infection, a total of 375 healthy controls, 219 HCV spontaneous recovered patients and 600 chronic HCV patients from Southeast China were recruited and genotyped in this study. And the relative mRNA levels of CTLA-4 in T cells were detected. Logistic regression analysis showed that rs231775 A allele was associated with significantly higher rate of spontaneous viral clearance in anti-HCV F antibody negative patients (adjusted OR = 0.512, P = 0.008), but allele A was related to higher mRNA level of CTLA-4 with the generation of HCV F protein. And rs5742909 T allele added up to the risk of HCV infection chronicity significantly in patients with the presence of HCV F protein (adjusted OR = 2.698, P = 0.003). Also, the rs5742909 CC genotype, along with the presence of HCV F protein, indicated a significantly higher CTLA-4 level than that in anti-HCV F antibody negative patients. The AG+AA genotype of rs3087243 significantly increased the susceptibility to HCV infection in subjects over 56 years old (adjusted OR = 1.595, P = 0.011). Genotype–genotype interaction between IL-28B rs12979860 and CTLA-4 rs3087243 was found to be significantly associated with increased susceptibility to HCV infection (adjusted OR = 1.509, P = 0.005). Haplotype analysis in CTLA-4 also showed significant association with the generation of HCV F protein. All these results indicated the importance of IL-28B and CTLA-4 polymorphisms and their associations with HCV F protein in the risk and chronicity of HCV infection in Chinese Han population in Southeast China. [ABSTRACT FROM AUTHOR]

Programmed cell death-1 (PD-1) is an important co-inhibitory molecule involved in the progression of chronic viral infections. To investigate the associations of three single nucleotide polymorphisms (SNPs) (rs10204525, rs2227982 and rs36084323) in PD-1 and a previously well-inquired SNP rs12979860 in IL-28B with the outcomes of hepatitis C virus (HCV) infection in Southeast China, a total of 375 healthy controls, 219 spontaneous resolved HCV patients and 600 chronic HCV patients were enrolled in this study. The generation of HCV F protein and PD-1 expression on T cells was determined. Multivariate logistic regression analysis showed no association of rs12979860 CC genotype with spontaneous clearance of HCV infection in our subjects. The generation of HCV F protein was significantly related to HCV infection chronicity, but no significant relationship was found between HCV F protein and SNPs in PD-1. The rs10204525 TT genotype was associated with an increased risk of HCV infection chronicity in age ⩽56 years subgroup (adjusted OR = 0.390, P = 3.8 × 10 −4 ). The C allele of rs10204525 played protective roles in females infected with HCV (adjusted OR = 0.608, P = 0.008). A significant higher percentage of PD-1 expression on T cells was observed in rs10204525 TT genotype when compared to CC genotype ( P = 0.047). Moreover, a significant genotype–genotype interaction between IL-28B rs12979860 CC and PD-1 rs10204525 TC + CC was found to be associated with higher rates of spontaneous clearance (adjusted OR = 0.689, P = 0.032). The combined effect of rs12979860 and rs10204525 was of great value in predicting the outcomes of HCV infection. These analyses showed the importance of IL-28B and PD-1 polymorphisms and their interactions in the outcomes of HCV infection in Chinese Han population in Southeast China. [ABSTRACT FROM AUTHOR]