GWAS identifying HLA‐DPB1 HLA‐DPB1 gene variants associated with responsiveness to hepatitis B virus vaccination in Koreans: Independent association of HLA‐DPB1*04:02 HLA‐DPB1*04:02 possessing rs1042169 G ‐ rs9277355 C ‐ rs9277356 A

摘要

Abstract Recently, HLA class II loci, including HLA‐DPB1 , have been reported to be associated with interindividual variance in the hepatitis B (HB) vaccine response. In this study, we investigated significant single nucleotide polymorphisms (SNPs) for anti‐HBs antibody levels in 6867 healthy Koreans using a genome‐wide association study (GWAS). In GWAS, the top 20 SNPs that showed significant association with anti‐HBs levels ( P ??1.0?×?10 ?29 ) all resided in HLA‐DPB1 . Utilizing PCR sequencing, we verified the relationship of the top 3 most significant SNPs (rs1042169, rs9277355 and rs9277356) from the GWAS and genotypes of HLA‐DPB1 with the HB vaccine response in Korean infants who received a scheduled vaccination. The DPB1*04:02 allele has G, C and A nucleotides for the 3SNP sites, and was significantly more frequent in responders than in nonresponders (10.9% vs 1.0%, P c ?=?0.018). DPB1*05:01 was significantly more frequent in nonresponders than in responders (49.0% vs 31.1%, P c ?=?0.018). In multivariate logistic regression, DPB1*04:02 showed a significant association with both vaccine response ( P ?=?0.037, OR?=?8.465) and high‐titre response ( P ?=?0.027, OR?=?9.860). The haplotypes rs1042169 G ‐ rs9277355 C ‐ rs9277356 A showed a significant association with a high‐titre response only ( P ?=?0.002, OR?=?2.941). In conclusion, DPB1*04:02 possessing rs1042169 G ‐ rs9277355 C ‐ rs9277356 A is an independent predictor of the HB vaccine response in Koreans.