In Taiwan, where HBV genotype B is endemic, CHB patients with the rs9277535 non-GG genotype have a higher chance of clearing HBsAg (37). Thus, the HLA-DP polymorphisms promoting HBV clearance may Volasertib leukemia predispose the host to clear genotype B HBV preferentially. However, the rs9277535 G allele is not or is weakly associated with HBV persistence in Caucasians (38, 39). This disparity might be due to the diversity in HBV genotype endemicity or in the SNP frequencies among different races. According to the NCBI database (http://www.ncbi.nlm.nih.gov/projects/SNP/), allelic frequencies of the HLA-DP polymorphisms differ greatly among races. C/G is the major allele of rs3077 and rs9277535 in the Asian population, but it is the variant allele in the European population.

This might be one of the reasons why HBV persistence is more frequent in Asians than in Europeans. In this study, we defined the wild-type nucleotides of HBV genotype B and genotype C from ASCs seropositive for HBeAg. The prevalence of C1653T, T1753C, A1762T/G1764A, and pre-S deletion mutations in HBV genotype C and A1762T/G1764A mutations in HBV genotype B increased successively along with HBV evolution, which was quite consistent with our previous meta-analysis (8), supporting the rationality of this definition. Although the HC- and HCC-related HBV mutations counterchanged at some nucleotides between genotype B and genotype C, the associations of these mutations with HCC risk were quite consistent for both genotypes (Table 3). This reflects the inherent law of HBV evolution since chronic HBV infection is established.

T1674C and G1719T mutations were protective factors for HCC in genotype B and risk factors for HCC in genotype C infections (Table 3), and the impacts of the A2875C, A2946G, and T3026C mutations were not consistent between genotypes B and C (Table 4). These findings reflect the diversity of the genetic and antigenic natures of the two HBV genotypes. We found that the frequencies of significant HBV mutations in the pre-S2 region of both genotypes were close to 0% in ASCs but reached approximately 100% in CHB patients, HC patients, and HCC patients. These significant mutations may be selected during acute exacerbation Brefeldin_A upon the ASC state and kept in subsequent steps of HBV evolution. This novel finding is of great clinical and public health significance. Associations between HLA class I genotypes/alleles and escape mutations in the HBV core gene have been investigated in chronic HBV infection (40, 41). However, associations of HLA-DP polymorphisms with HBV mutations have not been reported. In this study, we found a group of disease-related HBV mutations whose frequencies were significantly affected by HLA-DP polymorphisms (Table 5).