Association Between SNPs In IL-10 Promoter And HBV Infection

Hepatitis B virus (HBV) infection can cause disease. The proceeding of disease and turnover show great difference. One can show with asymptomatic HBV carriers to cryptic hepatitis, acute hepatitis, chronic hepatitis, liver cirrhosis and primary hepatocellular carcinoma. The variable pattern and clinical outcome of the infection were mainly determined by virological itself factors, host immunological factors and genetic factors as well as the interventional factors. IL-10 possesses extensive immunizing vigour. It is a immunoregulation cytokine with immunological inhibition and immunostimulation dual effects. It playes central action in body's immunoregulation. So the change of IL-10 level, can affect susceptibility to virus hepatitis, severity and sensibility to therapy, and so on. The secretary level of IL-10 is determined by genetic factor at a large degree. IL-10 promoter takes responsibility in combination with regulatory factor for gene expression and thereby promoter SNPs can affect transcription and expression of IL-10 gene directly. SNP has hereditary stability, it has been extensively utilized as a kind of genetic marker. As for HBV infection, SNPs in promoter region of IL-10 are the hot spot of study. Not only can they affect expressed regulation of IL-10 vivo alone, but also they can control the change of IL-10 level as linked pattern, that is to shape different haplotype. So the study on gene polymorphism in promoter region of IL-10 in patients with hepatitis B has significance. This study applied case-control association analysis, aimed at identifying the correlation between gene polymorphism in IL-10promoter and turnover after HBV infection, severity of hepatitis B, and patients'sensitivity to adefovir. So can expect to clear the pathogenesy of hepatitis B and provide necessary theoretical evidence for more effective preventing and treating HBV infection.Subjects were divided in to three groups as patients, self limiting infection and normal control. All subjects in these three groups were all Han people in the northern part of China, and they could match each other in sex and age. The SNPs of IL-10-592 and -1082 were detected and genotyping was performed using PCR-RFLP. And observing the distribution of different genotype in different groups, finally carrying out association analysis with statistically means.The following are the major results obtained in this study.1. The genotypic distributions of IL-10-592 and IL-10-1082 SNP in all subjects were not deviated from the H-W equilibrium (P>0.05).2. AA,AC and CC genotypes of IL-10-592 locus were detected in patients,self limiting infection and normal control groups. Mutant gene frequency was found to be 55.56%,64.67% and 55.33% among the different groups respectively. Distribution of genotype had significant difference between patients and normal control, but no significant difference was observed between self limiting infection and normal control, and between patients and self limiting infection. Comparing group of patients with group of normal control, AC genotype had more risk to hepatitis B than CC, the risk of AC was 2.412 times bigger than that of CC. We couldn't exclude the possible correlationbetween the polymorphism of IL-10-592 and the turnover after HBV infection. 3. AA,AG and GG genotypes of IL-10-1082 locus were detected in patients and self limiting infection groups. GG genotype was not seen in normal control group. Mutant gene frequency was 3.68%,6.17% and 11.11% among the different groups respectively. Genotype distribution had significant difference among the patients and normal controls, and self limiting infection and normal control group, but no significant difference was observed among the patients and self limiting infection group. Probably there were not correlation between the polymorphism of IL-10-1082 and the turnover after HBV infection.4. There was no correlation between the polymorphism of IL-10-592 and the level of serum transaminase, the serum virus load and the pathologic change of liver.5. The analysis of the polymorphism of IL-10-592 and sensitivity to adefovir showed that, there probably was a correlation in the aspect of aminotransferase recovered after medication, but no correlation in the aspect of the dynamic change of DNA.In a word, It is difficult to exclude the possible correlation between the SNPs in the promoter of IL-10 and the HBV infection. There was probably a correlation between the gene polymorphism of IL-10 and the improvement of inflammatory reaction in liver after treating with adefovir. These findings will contribute to explain the immunological mechanism of hepatitis B, and will benefit to predict individual onset risk, and to choose effective treatment at gene level.