Strong influence of human leukocyte antigen-DP variants on response to hepatitis B vaccine in a Japanese population.

Genome-wide association studies (GWASs) have reported that human leukocyte antigen (HLA) variants are associated with chronic hepatitis B, spontaneous hepatitis B virus (HBV) clearance, and response to hepatitis B vaccine. Single nucleotide polymorphisms (SNPs) in HLA-DP (rs9277535 and rs3077) and HLA-DQ (rs2856718 and rs7453920) have been repeatedly associated with chronic hepatitis B and spontaneous HBV clearance. However, the data on the SNPs associated with response to hepatitis B vaccine are inconclusive. The objective of this study was to determine whether these four HLA SNPs that have been identified as risk loci for chronic HBV infection are associated with response to hepatitis B vaccine in a Japanese population. We enrolled 278 medical students who received hepatitis B vaccination and measured anti-hepatitis B surface (HBs) antibody titers 1month after a three-dose vaccination series. We found that rs9277535 and rs3077 in HLA-DP were strongly associated with response to hepatitis B vaccine (odds ratio [OR]=0.31 and 0.32, P=0.004 and 0.010, respectively). These two SNPs were significantly associated with anti-HBs titers in an allele-dependent manner. On the other hand, rs2856718 and rs7453920 in HLA-DQ were not associated with response to hepatitis B vaccine. These results indicate that rs9277535 and rs3077 in HLA-DP are the major determinants of response to hepatitis B vaccine, whereas rs2856718 and rs7453920 in HLA-DQ have little effect on the immune response to hepatitis B vaccine.