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Host genetics play a vital role in determining clinical outcomes of hepatitis B virus (HBV) infection. To identify novel susceptibility loci to HBV progression, we carried out a genome-wide association study with DNA pooling. This study assessed the relationship between 8 highly-ranked SNPs selected from our DNA pool and disease progression of HBV infection in two independent case-control studies. The first population included 628 asymptomatic HBV carriers (AsC) and 1729 progressed HBV carriers recruited from Hubei Province in south China. The second population was composed of 226 AsC and 215 progressed HBV carriers recruited from Shandong Province in north China. Of the 8 SNPs, variant rs11866328 (G/T), located in the glutamate receptor ionotropic N-methyl D-aspartate 2A (GRIN2A) gene, was replicated and had significant associations with disease progression of HBV infection in the DNA pooling stage both in the Hubei (OR 1.65; 95% CI 1.34,2.02; p=1.96 × 10(-6); additive model), and in the Shandong (OR 1.73; 95% CI 1.14,2.65; p=1.00×10(-2); additive model) population. Polymorphism rs11866328 in the GRIN2A gene might be a genetic variant underlying the susceptibility of HBV carriers to disease progression.

BackgroundHuman 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 populations.Methodology/principal findingsTwo 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 2 805 cases and 1 796 controls. 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(-8) at rs2395309; P = 8.37×10(-3)∼2.68×10(-10) at 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).ConclusionsOur 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.