P061 Association of HLA class II genes with response to hepatitis B vaccine in Japanese

Abstract

Aim Associations of SNPs located in the HLA class II region with responses to booster hepatitis B vaccination have been identified in Asian populations. However, there have been no reports to identify the associated gene(s) with response to hepatitis B vaccination by means of genome-wide association study (GWAS). Methods A total of 1253 Japanese adult healthy volunteers, who were vaccinated in three doses (0.25 mL) at 0, 1, and 6 months with recombinant absorbed hepatitis B vaccine (Bimmugen®, Kaketsuken, Kumamoto, Japan), were genotyped using Affymetrix Axiom Genome-Wide ASI 1 Array. After sample filtering by identity-by-descent and principal component analysis, eighteen and thirty-six individuals were removed from further analysis, respectively. In addition, six individuals who were anit-HBc positive (>1.0 S/CO) were removed in this study. Finally, the remaining 1193 individuals were categorized into three groups: low responder, HBsAb ⩽ 10 mIU/mL ( n = 107); intermediate responder, 10 mIU/mL n = 351); high responder, HBsAb ⩾ 100 mIU/mL ( n = 735). HLA imputation was applied to determine HLA alleles using genome-wide SNP typing data of 1193 individuals. The diplotype of each individual was estimated using PHASE software. Results A genome-wide significant association was detected at a SNP located in the HLA-DR region in the SNP-based GWAS. Moreover, HLA genotyping-based analysis identified that a DRB1-DQB1 haplotype and a DPB1 allele were independently associated with low response to the hepatitis-B vaccine. Conclusions The present study demonstrated that specific HLA class II alleles and haplotypes are significantly associated with response to HB vaccination in the Japanese population.