BACKGROUND The expression of macrophage inhibitory factor-1 (MIC-1) is increased in peripheral blood of patients with chronic hepatitis and liver cirrhosis. However, whether MIC-1 gene polymorphism is correlated with relevant diseases is not yet reported. AIM To explore the correlation between gene polymorphism in MIC-1 exon region and chronic hepatitis C virus (HCV) infection. METHODS This case-control study enrolled 178 patients with chronic hepatitis C (CHC) in the case group, and 82 healthy subjects from the same region who had passed the screening examination comprised the control group. The genotypes of rs1059369 and rs1059519 loci in the MIC-1 gene exon were detected by DNA sequencing. Also, the MIC-1 level, liver function metrics, liver fibrosis metrics, and HCV RNA load were determined. Univariate analysis was used to compare the differences and correlations between the two groups with respect to these parameters. Multivariate logistic regression was used to analyze the independent relevant factors of CHC. RESULTS The plasma MIC-1 level in the CHC group was higher than that in the control group ( P < 0.05), and it was significantly positively correlated with alanine aminotransferase, aspartate aminotransferase (AST), type III procollagen N-terminal peptide (known as PIIINP), type IV collagen, and HCV RNA ( P < 0.05), whereas negatively correlated with total protein and albumin ( P < 0.05). The genotype and allele frequency distribution at the rs1059519 locus differed between the two groups ( P < 0.05). The allele frequency maintained significant difference after Bonferroni correction ( Pc < 0.05). Logistic multiple regression showed that AST, PIIINP, MIC-1, and genotype GG at the rs1059519 locus were independent relevant factors of CHC ( P < 0.05). Linkage disequilibrium (LD) was found between rs1059369 and rs1059519 loci, and significant difference was detected in the distribution of haplotype A-C between the CHC and control groups ( P < 0.05). Meanwhile, we found the MIC-1 level trend to increase among rs1059519 genotypes ( P = 0.006) and the level of MIC-1 in GG genotype to be significantly higher than CC genotype ( P = 0.009, after Bonferroni correction). CONCLUSION Plasma MIC-1 level was increased in CHC patients and correlated with liver cell damage, liver fibrosis metrics, and viral load. The polymorphism at the MIC-1 gene rs1059519 locus was correlated with HCV infection, and associated with the plasma MIC-1 level. G allele and GG genotype may be an important susceptible factor for CHC.
The expression of macrophage inhibitory factor-1 (MIC-1) increases in patients with chronic hepatitis C (CHC), but whether MIC-1 level and its polymorphism affect the antiviral efficacy of CHC has not yet been reported. The present study aimed to investigate the association between MIC-1 polymorphism and antiviral efficacy in patients with CHC genotype 1b (CHC 1b). A total of 171 patients with CHC1b were recruited. The polymorphisms of rs1059369 and rs1059519 in MIC-1 were detected by DNA sequencing. All patients received a standard dose of polyethylene glycol interferon + ribavirin (PR regimen), and divided into response, nonresponse, sustained virological response (SVR), and non-sustained virological response (NSVR) groups based on HCV RNA levels. The genotype distribution of the two single nucleotide polymorphisms (SNPs) did not differ between the response and nonresponse groups, SVR and non-SVR groups. However, the level of MIC-1 was positively correlated with ALT, AST, PIIINP, CIV, and HCV RNA (P < 0.05). Compared to before treatment, the level of MIC-1 in plasma was significantly decrease in the response group but not in the non-responsive group. Our results suggest that the level of MIC-1 in CHC1b is correlated with liver cell injury, liver fibrosis index, and viral load. However, the polymorphism of rs1059369 and rs1059519 may have negligible impact in expression of MIC-1 and efficacy of antiviral therapy in CHC patient.
Hepatitis C virus (HCV) is a major public health concern in developing countries. Pathogenesis of hepatitis C infection is poorly understood. Previously, we found higher Interferon Regulatory Factor-3 (IRF-3) expression in HCV-infected patients. However, the effect of IRF-3 polymorphism on the incidence of HCV infection and antiviral efficacy has not been sufficiently evaluated. In this retrospectively study, 178 patients with chronic hepatitis C (CHC) and 82 matched healthy controls were enrolled. All patients received standard dose of polyethylene glycol interferon and ribavirin (PR regimen), and were assigned to response, non-response, sustained virological re-sponse (SVR), and non-sustained virological response (NSVR) groups based on their content of HCV RNA. Gene polymorphisms were detected by DNA sequencing, and the plasma IRF-3 and IFN-β levels were measured by ELISA to assess the impact of IRF-3 gene variations and contents on the risk of HCV infection and antiviral efficacy. The results showed that plasma contents of IRF-3 and IFN-β were significantly different between the CHC and control groups, the response and non-response groups, and the SVR and non-SVR groups. rs2304206 C > T but not rs2304204A > G was associated with increased risk for CHC, and reduced antiviral efficacy between both response groups and SVR groups. Haplotype GT type suffered negative consequence be-tween the CHC and control groups, the responder and non-responder groups, and the SVR and non-SVR groups. The content of IFR-3 in CT genotype of rs2304206 was higher than that in CC genotype. In conclusion, the polymorphism of IFR-3 affects the plasma levels of IFR-3 and associated with HCV infection and interferon antiviral efficacy, where the T allele of rs2304206 may be a susceptibility factor for CHC and adversely impact interferon antiviral response.
Background Hepatitis C virus (HCV) is a major public health concern in developing countries. Pathogenesis of hepatitis C infection is poorly understood. Previously, we found higher Interferon Regulatory Factor-3 (IRF-3) expression in HCV-infected patients. However, the effect of IRF-3 polymorphism on the incidence of HCV infection and antiviral efficacy has not been sufficiently evaluated.Methods We retrospectively enrolled 178 patients with chronic hepatitis C (CHC) and 82 matched healthy controls between 2016 and 2019 at the Second Hospital of Wenzhou Medical University, China. All patients received a standard dose of polyethylene glycol interferon + ribavirin (PR regimen), and were divided into the response, non-response, sustained virological response (SVR), and non-sustained virological response (NSVR) groups based on their HCV RNA levels. Gene polymorphisms were detected by DNA sequencing, and the plasma IRF-3 and IFN-β levels were measured by ELISA to assess the impact of IRF-3 gene variations and contents on the risk of HCV infection and antiviral efficacy.Results Plasma contents of IRF-3 and IFN-β were significantly different between the CHC and control groups, the response and non-response groups, and the SVR and non-SVR groups (p<0.05). rs2304206 C>T but not rs2304204A>G was associated with increased risk for CHC (OR= 2.35 (95% CI: 1.30 to 4.24), p = 0.004), and reduced antiviral efficacy between both response groups (OR= 1.86 (95% CI: 1.06 to 3.24), p = 0.028) and SVR groups (OR= 1.79 (95% CI:1.05 to 3.06), p = 0.030). Haplotype GT type suffered negative consequence between the CHC and control groups, the responder and non-responder groups, and the SVR and non-SVR groups (p=0.004, 0.028, 0.030). The content of IFR-3 in CT genotype of rs2304206 was higher than that in CC genotype.Conclusion The polymorphism of IFR-3 affects the plasma levels of IFR-3 and associated with HCV infection and interferon antiviral efficacy, where the T allele of rs2304206 may be a susceptibility factor for CHC and adversely impact interferon antiviral response.
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