| Hepatitis C is one of the most common infectious liver diseases worldwide and leads to a significant global health burden, especially in parts of Asia and Africa. The World Health Organization (WHO) estimates that approximately3%people (170million) have been infected with hepatitis C virus (HCV), and about80%of these will develop chronic hepatitis, cirrhosis and hepatocellular carcinoma. The prevalence of HCV infection is different around the world, which is reported to be22%in Egypt, and3.2%in China. HCV is an enveloped virus containing a positive-sense single-stranded RNA genome of approximately9.5kb. The viral genome consists of a lengthy5’untranslated region (UTR), a long open reading frame encoding a polyprotein precursor of approximately3011amino acids, and a short3’UTR. Viral structural proteins include a nucleocapsid core protein (C) and two envelope glycoproteins, E1and E2. The E1and E2is the most highly unconserved part of the HCV genome. HCV is currently divided into6genotypes, and each genotype is further divided into a variable number of subtypes. Genotypes differ from each other by31%to33%at the nucleotide level, whereas subtypes within the same genotype differ from each other by20%to25%. In addition to providing epidemiological information, the genotyping assay is clinically important because the result could affect treatment decisions. For example, genotypes1and4are more resistant to pegylated interferon-a and ribavirin combination therapy than genotypes2.Numerous studies confirm that genetic factors play a central role in determining clinical phenotype, and the vast majority of these studies have focused on the role of the genes in the HLA/MHC region. Effective presentation of viral antigens to CD4+T cells and CD8+T cells by HLA class Ⅱ and class Ⅰ molecules respectively, is the key regulation of optimum immune response against viral infection, and further dictates viral clearance or persistence. Recently, a genome-wide association study (GWAS) demonstrated that genetic variants in the HLA-DP locus were strongly associated with chronic hepatitis B in Japanese and Thai populations. Han Chinese constitute about92%of the population of China,98%of Taiwan,78%of Singapore, and about20%of the world population. However, the association of some of these HLA-DP SNPs with HCV infection has not been verified.In this study, we investigate the distribution of hepatitis C virus(HCV) genotypes in Jiangsu province and its relationship to infectious routes and conditions of hepatic function. Besides, we also analysis the association study of polymorphisms of HLA-DP with HCV infection.Part I Study on Hepatitis C virus genotyping in patients infected with HCV by different routes in Jiangsu provinceHCV is an enveloped virus containing a positive-sense single-stranded RNA genome of approximately9.5kb.The viral genome consists of a lengthy5’untranslated region (UTR), a long open reading frame and a short3’UTR. HCV is currently divided into six genotypes, and each genotype is further divided into a variable number of subtypes. In addition to providing epidemiological information, the genotyping assay is clinically important because the result could affect treatment decisions. Thus, we recruited505patients to analysis the distributions of genotype analysis from May2006to December2019in Jiangsu province. [Objective] To investigate the distribution of hepatitis C virus(HCV) genotypes in Jiangsu province and its relationship to infectious routes and conditions of hepatic function.[Methods]The HCV genotypes of patients were determined by PCR products of5’ untranslated region (UTR) digested with restriction endonucleases, and the relationships of genotype to age, gender, liver function and infectious routes were analyzed.[Results]1. Detection of HCV genotypesAmong505HCV RNA-positive serum samples there were8(1.6%) genotype la,348(68.9%)1b,24(4.8%)2,40(7.9%)3and85(16.8%) other genotypes respectively.2. HCV genotype in different groupsThe HCV genotype distribution was not different among the subjects of different groups which were classified by sex and age (Page=0.445, P sex=0.083); The ALT and AST levels did not show statistically significant differences among the patients infected with different HCV genotypes (PALT=0.781, PAST=0.217).3. HCV genotype in different infected waysIt was significantly different among the patients infected with HCV by different ways(P<0.001).[Conclusions]Type lb was the predominant HCV genotype in Jiangsu Province and HCV1a genotype showed the epidemic trend in mainland of China. HCV genotypes showed a relationship to infectious routes. Part II Study of Polymorphisms of HLA-DP with Hepatitis C Virus infectionHepatitis C virus (HCV), a single-stranded RNA virus (ssRNA), is one of the most common cause of cirrhosis, hepatocellular carcinoma (HCC), which are serious end stage of live diseases worldwide. Single nucleotide polymorphisms (SNPs) represent a natural genetic variability at high density in the human genome. Recent study using genome-wide association studies (GWAS) have shown SNPs in HLA-DP are associated with persistence of HBV infection. Since HLA-DPA1and HLA-DPB1code the functional subunit of major histocompatibility complex (MHC) class II, these data may suggest possible interactions between virus and host immunity.With respect to the pivotal roles of HLA-DP polymorphisms in infection disease, we explored that HLA-DP polymorphisms may be associated with HCV infection in mainland Chinese population.[Objective] This study aimed to assess the relationship between HLA-DP gene polymorphisms and the susceptibility of HCV infection among high-risk populations in Jiangsu Province.[Methods]Three HLA-DP variants of rs3077, rs9277535and rs2395309were genotyped in1653subjects including268self-limited HCV persistent infections,401persistent HCV infections and984healthy controls using Taqman-MGB.[Results]1. The characteristics of401HCV persistent carriers,268HCV clearance subjects and984uninfected controls are recruited. Briefly, no significant differences were observed in the distribution of age and sex. However, there were significant difference among the three groups in ALT, AST, high-risk behaviors and viral genotypes (all P<0.001). All the SNPs were in Hardy-Weinberg equilibrium in controls (all P>0.05).2. Between HCV infected subjects (HCV persistent carriers and HCV natural clearance subjects) and uninfected subjects, the genotypes CT and GG of rs3077increased the risk of HCV infection (OR=1.31,95%CI=2.05-2.64;OR=1.93,95% CI=1.36-2.24),the genotypes GA and AA of rs2395309increased the risk of HCV infection(OR=1.29,95％CI=1.03-1.61；OR=1.89,95%CI=1.34-2.68).Besides, compared with HCV natural clearance subjects carrying GG of rs9277535,those with GA and AA genotypes had an increased risk for chronic infection(OR=1.54,95%CI=1.05-2.28；OR=1.62,95%CI=1.01-2.60).3.The haplotype analysis among females found that haplotype TAA was associated with HCV susceptibility(OR=1.31,95%CI=1.09-1.55).[Conclusions]This study indicated that two SNPs in TLR7are associated with HCV clearance and susceptibility to HCV infection. |
PDF Full Text Request