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Study On Hepatitis C Virus Genotyping And The Association Of IL-18 Gene Polymorphism With Hepatitis C Virus Infection

Posted on:2012-08-24Degree:MasterType:Thesis
Country:ChinaCandidate:Y LiuFull Text:PDF
GTID:2154330335981573Subject:Epidemiology and Health Statistics
Abstract/Summary:PDF Full Text Request
HCV infection is a common blood-borne transmitted disease, it is estimated that 130 million people are infected with HCV all over the world, and the natural infection rate of HCV in china is 3.2%. Infection of HCV would lead to hepatitis C, which progressed rapidly and resulted in cirrhosis and hepatocellular carcinoma. HCV is an enveloped, positive-strand RNA virus belonging to the Flaviviridae family. At least six major genotypes of HCV, each comprising multiple subtypes, have been identified worldwide with the different regional distributions. Clinical manifestations and response to interferon-αtreatment differed from the infection of HCV with different genotypes. So it is very significative to study the molecular epidemiology of HCV among IDUs infected with HCV in Jiangsu province. For this reason, we carry out a population-based molecular epidemiological study to investigate the distribution of HCV genotype in Jiangsu province. Objective: to investigate the distribution of HCV genotype among IDUs in Jiangsu province, the results of which will provide basis for the diagnosis, prevention of HCV infection.Methods: 552 anti-HCV positive sera samples from drug users was detected by FQ-PCR, the genotype of HCV was conducted on the positive samples using type specific primers deduced from the core region of HCV RNA by RT- PCR.Results:1 Detection of HCV genotypesOf total 552 patients, 259 were HCV RNA positive in which 187 samples were genotype 1b (72.2%), 24 samples were genotype 2a (9.3%), 1 samples had genotype 1a (0.4%), 1 samples had genotype 2a (0.4%), 44 samples was mixed types (17.0%) and genotype could not be determined in 2 samples(0.8%).2 HCV genotype in different sex groupsSignificant difference was found in HCV genotypes distribution between female patients and male ones (P=0.017). Distribution difference of 1b type and non-1b type was also found significance between them (P=0.034). But no siginificance was found in the distribution of single type and mixed type(sP=0.954).3 HCV genotype in different age groupsThere was no significance in HCV genotype distribution in different age groups. Either in 1b and non-1b type, single and mixed types.4 HCV genotype in different level of ALT groupsThere was significance in genotype distribution between different level of ALT(P=0.006); there was also statistics difference on the infection distribution between the single and mixed,1b type and non-1b type(P=0.014,P<0.001).5 The relationship between HCV genotypes and HCV RNA loadHCV RNA levels between different genotypes was significantly different (P<0.001). Conclusion: The predominant genotype of HCV in drug users of Jiangsu province is lb,with other genotypes coexisting. The genotype distribution lies between the North and South China. There is sufficient evidence to suggest that the HC progression is multifactorial, including viral, host immunological and genetic factors. Host genetic factor plays an important role in the pathogenesis of HCV infection. The human Il-18 gene is located on 11q23.1 and called an IFN-γ-inducing factor. IL-18 is intimately involved in both the innate and adaptive immune responses and plays a significant role in defense against viral infection. The aim of this study is to explore the association between IL-18 polymorphism and the susceptibility and outcomes of HCV infection.[Objective]: The aim of this study is to explore the association between IL-18 polymorphism and the susceptibility and outcomes of HCV infection.[Methods]: Between December 2006 and March 2009, a total of 1200 drug users from Nanjing compulsory rehabilitation centers were categorized into two different groups:①HCV-infected group(n=522), including a HCV persistent infection group and a HCV spontaneously recovered group.②HCV-uninfected group(n=648) matched to the HCV-infected cases by age, gender, and geographical area. Three polymorphic sites in the IL-18 gene were analyzed by real time–PCR, using a predevelopment TaqMan-MGB allele discrimination assay. All analyses were performed with SPSS13.0 software.[Results]:1 Comparison of general characteristicsThere was no significant difference in the distributions of age and gender among the cases and controls ( P=0.136 , P=0.135 ) , suggesting that our frequency-matching was adequate, but significant difference regarding the level of ALT and AST were found between the two groups(P<0.001).2 The distribution in cases and controls of SNPs of IL-18 We analyzed three SNPs of IL-18, after adjustment for age, sex, and ALT. The variants of -656G>T and -137G>C were negatively associated with the risk of HCV. The variants genotypes of +105A>C were associated with lower HCV risks [adjusted ORs (95%CI) = 0.67(0.51-0.87), 0.21(0.08-0.55)], compared with the wild-type homozygote respectively.3 Stratified analysis of +105A>CIn stratified analysis, +105A>C CC genotypes might be protective factors in male,middle age group and ALI>40U/L individuals [adjusted ORs(95%CI)=0.43(0.27-0.68),0.69(0.52-0.92), 0.38(0.24-0.61)],compared with the wild-type homozygote respectively. +105A>C AC genotypes also might be protective factors in female,middle age group and ALI>40U/L individuals [adjusted ORs(95%CI) = 0.24(0.08-0.72), 0.25(0.08-0.74), 0.16(0.04-0.55)],compared with the wild-type homozygote respectively.4 The distribution in the recovered group and persistent group of SNPs of IL-18The three SNPs of IL-18 were analyzed between the recovered group and persistent group. Only +105A>C polymorphism was shown to present significant difference between the two groups. The +105A>C genotypes was associated with a significantly decreased risk of HCV persistent [adjusted ORs(95%CI)0.61 (0.40-0.92)],compared with the wild-type homozygote respectively.[Conclusion]: This study suggested that the +105A>C position polymorphisms of IL-18 gene might be associated with the susceptibility of HCV infection. Moreover, AC genotype at position +105A>C may be closely linked to HCV clearance.
Keywords/Search Tags:Hepatitis C virus, HCV genotype, IL-18, SNP, cytokine
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