Association Of Antigen Processing And Presentation Related Gene HLA-DM Polymorphism With The Outcome Of HCV Infection Among High Risk Population

Section 1Epidemiological survey on the HCV infection among former paid blood donors in partial region of Jiangsu provinceForm 1980s to 1990s, some illegal and commercial blood centers were founded in some areas. These nonstandard behaviors of blood donation led to the spread of hepatitis C virus and other blood transmission diseases to blood donors. After previous investigation, our group knew there have thousands of paid blood donors reside in a town of Zhenjiang City. Most of these people sold their blood with the method of plasmapheresis from 1989 to 1993, and also some people had the history of whole blood donation. Most of them were housewives and resided in the town for a long time. Meanwhile they had never receipt any HCV detection and antiviral treatment.[Objectives] We aim to investigate the situation of HCV infection and its influence factors among paid blood donors in Zhenjiang City and provide some scientific basis for the treatment to these HCV infected residents.[Methods] A total of 582 paid blood donors in 9 villages of this town, who donate their blood around 1990s, were included in this study with the using of the specialized questionnaires. We collected 5 ml blood sample of each people to detect HCV antibody and other biochemical indicators. After the building of database, we analyzed the data using the software of SPSS 13.0.[Results] The prevalence of HCV infection among these paid blood donors was 39.2%(228/582). There had no statistic difference in the prevalence of HCV infection between different gender, age, education level and family income groups (P>0.05). Both the ALT and AST level of HCV-antibody positive people were higher than these HCV-antibody negative people. The risk of HCV infection among the people with the history of donating whole blood was much higher than the people without this history (OR=11.75,95% CI=3.56～38.80). The risk of HCV infection among the people with the history of donating plasma was also much higher than the people without this history (OR=27.12,95%CI=8.58～151.26). In addition, with the increasing of the number of whole blood and/or plasma donation, the risk of HCV infection was also raise. Multivariate logistic regression analysis indicated that the history of donating plasma and the number of donating plasma were the risk factors of HCV infection among paid blood donors.[Conclusion] The prevalence of HCV infection among paid blood donors is relatively high, which is due to the nonstandard blood collection, especially plasma collection. The detection, treatment and administration for these blood donors should be enhanced.Section 2The association of HLA-DM gene polymorphism with the outcome of HCV infection among high risk populationCurrently, about 170 million people had ever infected hepatitis C virus all over the world, including 40 million Chinese people. Hepatitis C virus is eliminated from the host in approximately 20 percent of acutely infected individuals but persists in the remaining 80 percent. Different individuals get different prognosis after infecting HCV. It not only related to the type of virus strain but also related to some gene polymorphism of the host. The polymorphism of some gene is maybe associated to the immunologic function of host and lead to different outcome of HCV infection.The antigen processing and presentation related genes were belonged to nonclassical MHC class Ⅱ gene, including HLA-DM, HLA-DO, LMP, TAP and Tapasin gene. HLA-DM plays an important role in the process of exogenous antigen presentation. It can favor the loading of high-affinity antigenic peptide and MHC Ⅱ molecules. The polymorphism of HLA-DM gene is maybe associated to the susceptibility to HCV and the outcome of HCV infection.[Objectives] The study aims to research the association of HLA-DM polymorphism with the susceptibility and the outcome of HCV infection and provide scientific basis to personalized treatment of HCV infection.[Methods] Genomic DNA of 690 patients with positive anti-HCV and 1105 uninfected controls were extracted from blood sample. Genotyping of HLA-DM gene polymorphism was performed using Taqman-MGB probe technology. After the building of the database, we used SPSS 13.0 software to analyze the association of the distribution of these genotypes with the susceptibility to HCV infection and the outcome of HCV infection.[Results] The frequencies of rs1063478 TT mutant genotype in HCV infected group was much lower than uninfected control group (OR=0.62,95%CI=0.40～0.95). It indicated that the carriage of TT genotype maybe could induce the susceptibility to HCV infection. The frequencies of rs3135029 AC heterozygous genotype and CC mutant genotype in chronic infection group were much lower than uninfected control group (OR=0.43,95%C=0.21～0.86; OR=0.46,95%CI= 0.23-0.90). The frequence of AC genotype in chronic infection group was lower than spontaneous clearance group(OR=0.35,95%CI=0.13～0.91). This result revealed the carriage of AC genotype could favor the clearance of HCV and decrease the risk of HCV persistent infection. Stratified Analysis showed that the frequnece of rs 1063478 TT genotype in HCV infected group was much lower than uninfected control group among female, people who was 40 to 60 years old, and drug use people(OR=0.01,95%CI=0.41～ 0.81; OR=0.39,95%C=0.20～0.77; OR=0.50,95%CI= 0.25-1.00). The frequnece of rs3135029 AC genotype in chronic infection group was much lower than spontaneous clearance group among female people, hemodialysis patients, and HCV type 1 infected patients(OR=0.20,95%CI=0.41～0.81; OR=0.10,95%C=0.01～0.67; OR=0.14,95%CI= 0.13～0.57). The frequnece of rs3135029 CC genotype in chronic infection group was much lower than spontaneous clearance group among HCV type 1 infected patients(OR=:0.27,95%CI=0.07～1.00). No difference in the distribution of rs1050391, rs23544 and rs2071556 genotypes among the uninfected control group, spontaneous clearance group and persistent infection group was found (P>0.05).[Conclusion] The single nucleotide polymorphism of rs1063478 was likely to associate with the susceptibility to HCV infection, and the polymorphism of rs3135029 was likely to relate to the outcome of HCV infection. However, further studies are needed to confirm our result.