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SNP rs7770370 in HLA ‐ DPB 1 loci as a major genetic determinant of response to booster hepatitis B vaccination: Results of a genome‐wide association study
Author(s) -
Wu TzuWei,
Chen ChuenFei,
Lai ShengKai,
Lin Hans Hsienhong,
Chu ChenChung,
Wang LiYu
Publication year - 2015
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12845
Subject(s) - single nucleotide polymorphism , human leukocyte antigen , allele , linkage disequilibrium , genetics , immunology , minor allele frequency , odds ratio , genome wide association study , snp , biology , genotype , virology , medicine , antigen , gene
Abstract Background and Aim Hepatitis B ( HB ) vaccination is highly effective in reducing the risk of hepatitis B virus infection. However, breakthrough and chronic hepatitis B virus infections in vaccinated subjects raised concern about its long‐term efficacy. The specific aim of the study was to explore the host genetic determinants of long‐term immunological memory against HB vaccination. Methods We conducted a case–control study nested in a cohort of HB booster recipients who had received primary HB vaccination during infancy but failed to reside an anti‐ HB s titers ≥ 10 mIU/mL at the age of 15–18 years. We used a genome‐wide single nucleotide polymorphism ( SNP ) array plate to scan autosomal chromosomes and assayed the human leukocyte antigen ( HLA ) ‐ DPB 1 genotype by sequence‐based techniques. Results We found that 10 of the 112 candidate SNP s ( P ‐value < 5.0 × 10 −5 ) clustered within a 47‐Kb region of the HLA ‐ DP loci. All the minor alleles of these HLA ‐ DP candidate SNP s were correlated with lower likelihoods of nonresponse to HB vaccine. There was a significant linkage disequilibrium between these HLA ‐ DP candidate SNP s and HLA ‐ DPB 1 protective alleles. Multivariate analyses showed that rs7770370 was the most significant genetic factor. As compared with rs7770370 GG homozygotes, adjusted odds ratios were 0.524 (95% confidence interval, 0.276–0.993) and 0.095 (95% confidence interval, 0.030–0.307) for AG heterozygotes and AA homozygotes, respectively. Conclusion Our results showed that rs7770370 was the most significant genetic factor of response to HB booster. The rs7770370 and nearby SNP s may also contribute to the long‐term immunological memory against HB vaccination.