The Research Of Association Of HLA-DPB1 Variant(rs9277542) With Different Outcomes Of Hepatitis B Virus Infection And Expression Of CISH,SOCS1,SOCS3 MRNA In Patients With Chronic Hepatitis B

ObjectiveTo investigate the association of HLA-DPB1 variant(rs9277542) with the different clinical outcomes of HBV infection. Materials and MethodsBlood samples were collected from 579 unrelated Chinese Han patients with persistent HBV infection, including 222 persistent asymptomatic HBV carriers(As C), 231 chronic active hepatitis B patients(CHB), 126 HBV-related liver cirrhosis patients(LC), and 344 cases of spontaneously recovered HBV were enrolled as control. SNapshot technique was performed on genotyping rs9277542 polymorphism in HLA-DPB1 gene. ResultsThere was a significant difference in the allele and genotype frequencies of rs9277542 between persistent HBV infection group and control(all P<0.0001). Taking CC genotype and C allele as reference, the odds ratio(OR) and 95% confidence intervals(95%CI) of the CT, TT genotypes and T allele were 0.53(0.39-0.71), 0.28(0.18-0.46), 0.54(0.44-0.66), respectively. However, no significant differences were found in the genotype frequencies for CC, CT and TT between CHB group and As C group(P>0.05). Stratification analysis showed that the frequencies of TT+CT genotype in LC group were significant higher than that in As C group and CHB group.(LC vs As C: P=0.016; LC vs CHB: P=0.018, respectively). ConclusionsThese findings indicate that rs9277542 variant in HLA-DPB1 could influence on spontaneous clearance of HBV infection and progression of patients with persistent HBV infection to HBV-related liver cirrhosis in Han Chinese population.Objective To observe the expression of CISH, SOCS1, SOCS3 m RNA and CD4+T lymphocyte subsets related cytokines in patients with chronic hepatitis B virus infection, and to evaluate the possible roles of these genes in HBV infection and the correlation of these genes with CD4+T lymphocyte subsets related cytokines.Materials and Methods Blood samples of 31 chronic hepatitis B(CHB) patients, 18 chronic asymptomatic HBV carriers(As C), and 18 healthy subjects(as normal control) were collected. The level of CISH, SOCS1 and SOCS3 m RNA expression in PBMCs(peripheral blood mononuclear cells) was detected by SYBR Green quantitative RT-PCR. The expression of IL-2, IL-4, IFN-γ, IL-10, IL-17 A and TGF-β in supernatant of PBMCs was measured by ELISA technique.Results Compared with control group, the expression of CISH/SOCS3 m RNA were significantly higher in CHB group(P<0.01), and the expression of SOCS3 m RNA in CHB group was higher than that of As C group(P<0.05), while the expression of SOCS1 m RNA was not statistically different between the three groups(P>0.05). The level of IL-4 of CHB group was higher than As C group(P<0.05), while compared with control group, CHB group showed a lower level of IFN-γ/IL-4 ratio(P<0.05), higher IL-4, IL-17 A and TGF-β expression(P<0.01), and As C group showed a higherlevel of IL-4 and TGF-β expression(P<0.05). In addition, the transcript level of SOCS1 m RNA in CHB group were correlated with CISH and SOCS3, and there was weakly positive correlation between SOCS3 and IFN-γ(P=0.008, P=0.002, P=0.037, respectively).Conclusions CISH and SOCS3 gene may be involved in the development of chronic hepatitis B virus infection, and have certain correlation with the changes of CD4+T lymphocyte subsets related cytokines.