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SNP rs7770370 in HLA-DPB1 loci as a major genetic determinant of response to booster hepatitis B vaccination: results of a genome-wide association study.

AbstractBACKGROUND 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-HBs 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)-DPB1 genotype by sequence-based techniques.
RESULTS:
We found that 10 of the 112 candidate SNPs (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 SNPs were correlated with lower likelihoods of nonresponse to HB vaccine. There was a significant linkage disequilibrium between these HLA-DP candidate SNPs and HLA-DPB1 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 SNPs may also contribute to the long-term immunological memory against HB vaccination.
AuthorsTzu-Wei Wu, Chuen-Fei Chen, Sheng-Kai Lai, Hans Hsienhong Lin, Chen-Chung Chu, Li-Yu Wang
JournalJournal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 30 Issue 5 Pg. 891-9 (May 2015) ISSN: 1440-1746 [Electronic] Australia
PMID25389088 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
Chemical References
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen
  • Hepatitis B Vaccines
Topics
  • Adolescent
  • Alleles
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Genome-Wide Association Study
  • Genotyping Techniques
  • HLA-DP beta-Chains (genetics)
  • Hepatitis B (immunology, prevention & control)
  • Hepatitis B Vaccines (immunology)
  • Humans
  • Immunization, Secondary
  • Immunologic Memory (genetics)
  • Infant
  • Male
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide
  • Risk
  • Time Factors

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