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Associations Between HLA-DP Genetic Variants And HBV-related Liver Diseases In Southern And Northern Han Chinese Populations

Posted on:2013-01-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:J LiFull Text:PDF
GTID:1114330371980583Subject:Molecular Biology and Biochemistry
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Background and purpose:Human leukocyte antigen DP(HLA-DP) locus has been reported to be associated with hepatitis B virus (HBV) infection in populations of Japan and Thailand. We aimed to examine whether the association can be replicated in Han Chinese.Methods:By using Tap-man MGB probe, two HLA-DP variants rs2395309 and rs9277535 (the most strongly associated SNPs from each HLA-DP locus) were genotyped in three independent Han cohorts consisting of 2805 cases and 1796 controls. The SPSS 17.0 Software was analyzed for the genotyped results. By using Arlequin 3.5 and haploview 4.2 software, we got the informations of population heterogeneity and haplotypes.Results:By using logistic regression analysis, these two SNPs in the HLA-DPA1 and HLA-DPB1 genes were significantly associated with HBV infection in Han Chinese populations (P=0.021-3.36×10-8at rs2395309; P=8.37×10-3-2.68×l0-10at rs9277535). In addition, the genotype distributions of both sites (rs2395309 and rs9277535) were clearly different between southern and northern Chinese population (P=8.95×10-5 at rs2395309; P =1.64×10-9 at rs9277535). By using asymptomatic HBV carrier as control group, our study showed that there were no associations of two HLA-DP variants with HBV progression (P =0.305~0.822 and 0.163~0.881 in southern Chinese population, respectively; P= 0.097~0.697 and 0.198~0.615 in northern Chinese population, respectively).Conclusion:Our results confirmed that two SNPs (rs2395309 and rs9277535) in the HLA-DP loci were strongly associated with HBV infection in southern and northern Han Chinese populations, but not with HBV progression.In a word, HLA-DP polymorphisms only participated in HBV infection, but did not participate in the carcinogenesis of HBV. Background and purpose:In order to support for the conclusion of the first part and get the latest paper, we performed a Meta-analysis for the HLA-DP polymorphism with HBV-related liver disease.Methods:After setting criteria, we retrieval the related papers by using Pubmed, google academic, Scirus and other literature database. The data, which is extracted from papers, were put into the Stata statistical software. Meta-analysis include Homogeneity test, building a fixed effects model/random effects model, detecting publication bias and other steps.Results:According to the screening criteria, we choose 10 papers from the initial 23. On the base of the different disease, the Meta-analysis were divided into three categories. First, the Meta-analysis of the relationship between HLA-DP and HBV clearance achieved the best results, and the two SNPs meet heterogeneity (P>0.05). Second, the results of HLA-DP and HBV-related liver cancer were negative, like the conclusion of the first part. Third, there was great heterogeneous in the Meta-analysis of HLA-DP and HBV infection. In rs9277535, the heterogeneity is I2=69.8%, P=0.002 in fixed effect model, and I2=63.9%, P=0.007 in random effects model.Conclusion:By Meta-analysis, we further confirmed that the strong associations between HLA-DP rs9277535, rs2395309 and HBV infections/Clear. Besides, some sites in the HLA-DP may be susceptible to HBV-related liver cancer, but the relationships require more study.
Keywords/Search Tags:HLA, SNP, HBVMeta-analysis, HBV, Association analysis
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