Study On The Relationship Between Cirrhosis Due To Hepatitis B Virus And HLA-DRB1 Allele Polymorphism

Hepatitis B virus (HBV) infection is an important global issue. China is a high HBV infection endemic areas of the world's chronic HBV infection by more than half. Human hepatitis B virus infection can lead to chronic asymptomatic HBsAg carrier(ASC), chronic hepatitis B (CHB), liver cirrhosis(LC) and hepatocellular carcinoma (HCC). Hepatitis B liver cell injury is caused mainly through a series of body immune response. Chronic HBV infection may be related with that the response of T cells to virus component is not adequate. Antigen-specific T cell receptor can identify with the HLA molecules on the antigen peptide.As binding force between peptides and HLA molecule is related with HLA genotypes, HLA genotype maybe one of the factors affecting the formation of chronic HBV infection.People are trying to find susceptibility gene of chronic hepatitis B to predict the determination of the development of diseases and guiding the treatment of chronic hepatitis B. The researches on the association between HLA-DRB1 and HBV infection have been launched in different areas and have made some progress, but the results in different parts of the crowd were not consistent, This study on HLA-DRB1 genotype and its association wtih hepatitis B and cirrhosis due to hepatitis B virus was made to investigate the relationship between them from the view of immune genetic point.In this paper, HLA- DRB1 genotyping was conducted in 32 case of chronic HBV infection and 39 health controls as well as 26 cirrhosis due to hepatitis B by using polymerase chain reaction - sequence specific primer method. All the patients were residents of Jilin district and belonged to Han nationality.HLA complex, that is aware of the most complex genetic systems, playes an important role on antigen identification, immune response and immune regulation, and is divided into three gene regions according to the different properties of their coding elements.Class I gene includs classics HLA-B, C, A gene loci and the newly discovered non-classical HLA classI including HLA-E, F, G, and other sites.ClassⅡgene includs HLA-DR, DQ, DP Gene Block, DN, DO pseudogene Block, and Block DM gene and non-MHC gene loci such as LMP1, LMP2, TAP1, TAP2. HLAⅡexpresses mainly on the surface of certain immune cells such as B cells, monocytes / macrophages, dendritic cells, activated T cells, the sperm and also a certain level of expression on vascular endothelial cell surface. HLAⅡmolecules associated with diseases are determined by its specific molecular structure.The study on HLA crystal structure showed that: At far membrane ofαandβchains of ClassⅡ, there is an antigen binding cleft, that critical amino acids related with diseases distributing in.The amino acid sequence is encoded by allele.Thus, polymorphism of HLAⅡallele leads to conformation of antigen binding cleft and the efficiency that antigen peptides presenting to T cells greatly different, which makes polymorphism of HLAⅡmost frequent and polymorphism of HLA-DRB1 most complex. ClassⅢgene includs gene encoding complement C4, C2B factor, tumor necrosis factor (TNFα, TNFβ), and heat shock protein (HSP70), and steroid 21-hydroxylase gene. There are two development after HBV infection: firstly, the immune status after cleaning up the virus; secondly, the persistent virus infection state as well as chronic HBV infection. The 2000 United States National Institutes of prevention and treatment of chronic HBV infection seminar divided infection of chronic hepatitis B into three periods, immune tolerance period , chronic hepatitis B and non-active or asymptomatic period with HBV carrier. Chronic HBV infection can lead to the results as follows:1.liver cirrhosis:chronic hepatitis B infection is the most common factor of liver cirrhosis. In Europe and the United States and Japan liver cirrhosis is mainly caused by the virus due to hepatitis C,while in China the number of positive HBV markers of serum is more than half of the patients with liver cirrhosis, and the incidence of chronic hepatitis B leading to liver cirrhosis was 0.4-14.2%.2.hepatoma: chronic HBV infection is the most important factor in liver cancer. China has almost 120 million HBsAg positive people,that has become the world's highest incidence of liver cancer and there are about 90 percent of liver cancer patients with HBV infection. Both liver cirrhosis and liver cancer will be a serious threat to human health and therefore it is of great significance clarifing mechanism of chronic HBV infection in order to prevent the occurrence that chronic hepatitis developing into cirrhosis or heptoma.The mechanisms HLAⅡmolecules affecting the outcome of HBV infection are still not understanded, relevant theories are as follows: 1.Molecular simulation hypothesis. 2.Receptor theory. 3. Immune response genes (Ir) theory. 4. Linkage disequilibrium theory. 5. Complement genetic defects or extended haplotypes linkage disequilibrium. 6.HLAI/HLAⅡantigen imbalance theory. Currently,related researches on chronic hepatitis B and HLA-DRB1 alleles have been made a leap development, but the results were different, possible reasons are as follows: (1)Ethnic differences, HLA allele frequencies have obvious race, ethnic differences. (2)There are different subt- ypes of the same HLA. Different types of alleles may also affect the outcome of consistency. (3) Different definition of control group, some control group are almost people to donate blood or the health check or do not check HBV infection markers in the "normal", which may include the crowd that have not yet exposed to HBV or HBV carriers. (4) Sample of study are different, compared to high HLA gene density, the volume of different samples will affect the test results.Expansion of samples will make the result of the research on HLA and HLA-related diseases come more real. Thus, the differences between the groups of region should be fully taken into account when it comes to the study on the relation between HBV infection and HLA - DRB1.We should better do research in the same region .Result:The frequency of HLA- DRB1*0701 allele in the CHB group was markedly higher than that in the normal control group (10.94 % vs 1.28 % , with significant correlation between them ,χ2=4.48,P<0.05;RR=10.64).No significant differences among the other alleles;The frequency of HLA- DRB1*0701 allele in the cirrhosis due to hepatitis B group was markedly higher than that in the normal control group (13.46 % vs 1.28% ,with significant correlation between them,χ2=6.044,P<0.05; RR=14).No signific- ant differences among the other alleles;There is no significant differences between the frequency of HLA-DRB1 allele in hepatitis B group and that in cirrhosisi due to hepatitis B group.The result shows that the high expression of HLA-DRB1 * 0701 allele is related with Jilin Han people with chronic HBV infection and polymorphism of HLA-DRB1 is an important factor that determining the clinical outcome of HBV infection. The result of this study has important theoretical and practical significance for understanding the function that HLA-DRB1 alleles plays on the incidence of chronic hepatitis B and the immune mechanisms of chronic hepatitis B and providing theoretical basis for geographical prevention of HBV infection related diseases.