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Hepatitis B virus (HBV) infection is a serious public health problem worldwide.Two common genetic variants (rs3077 and rs9277535) of Human Leukocyte Antigen DP (HLA-DP) have been reported to be associated with persistent HBV infection in populations of Japan and Thailand.To confirm whether the association can be replicated in Chinese populations, an independent case-control study were conducted, and two polymorphisms (rs3077 and rs9277535) were genotyped using the TaqMan SNP genotyping assay in 282 persistent chronic HBV carriers and 64 spontaneously HBV recovered carriers.To provide a more definitive conclusion, a meta-analysis combining and summarizing 5 studies was performed by random-effects model using the DerSimonian and Lairds method.By using logistic regression analysis with adjustment for covariates, including age, sex, and alcohol consumption, the results of our independent case-control study showed that the minor alleles homozygote (AA genotype) of rs3077 and rs9277535 was significantly associated with decreasing risk/protection of HBV persistent chronic infection (for rs3077: P=0.0017, OR=0.29, 95%CI =0.13-0.62; for rs9277535, P=0.0004, OR =0.26, 95%CI =0.12-0.54).The results of meta-analysis pooling all eligible studies also showed that rs3077-A and rs9277535-A alleles were associated with an increased clearance rate to HBV infection (rs3077: OR =0.57, 95%CI=0.44-0.75; rs9277535: OR =0.56, 95%CI=0.47-0.63).These results further confirmed the strong influence of HLA-DP gene variants on risk of spontaneous HBV clearance from persistent HBV infection.Both A alleles of HLA-DP SNP rs3077 and rs9277535 showed strong protective effects for spontaneous HBV clearance from persistent HBV infection in the Han Chinese population.