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

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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%, Pc = 0.018). DPB1*05:01 was significantly more frequent in nonresponders than in responders (49.0% vs 31.1%, Pc = 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.

Original languageEnglish
Pages (from-to)1318-1329
Number of pages12
JournalJournal of Viral Hepatitis
Volume26
Issue number11
DOIs
StatePublished - 1 Nov 2019

Keywords

  • HLA-DPB1
  • Korean
  • hepatitis B virus
  • vaccine response

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