Source Department of Epidemiology and biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.

Recent genome-wide association studies showed that four single-nucleotide polymorphisms (SNPs) in HLA-DP (rs3077and rs9277535) and HLA-DQ (rs2856718 and rs7453920) were associated with chronic hepatitis B virus (HBV) infection in Japanese populations. More than 75% of the hepatocellular carcinoma (HCC) patients are attributable to persistent infection of HBV, especially in China. We genotyped these four SNPs in1300 HBV-positive HCC patients, 1344 persistent HBV carriers and 1344 persons with HBV natural clearance from Southeast China to further test the associations of HLA-DP/DQ variants and with risk of both HBV clearance and HCC development. Logistic regression analyses showed that HLA-DQ rs2856718 significantly decreased host HCC risk, while three SNPs were associated with HBV clearance (HLA-DP rs9277535, and HLA-DQ rs7453920 and rs2856718). In addition, HLA-DP rs3077 showed an approaching significant effect on susceptibility to HBV persistent infection and HCC development when considering multiple testing adjustments. Taken together, we reported for the first time that genetic variants in the HLA-DP and HLA-DQ loci may be marker SNPs for risk of both HBV clearance and HCC development.