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-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.
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Authors | Tzu-Wei Wu, Chuen-Fei Chen, Sheng-Kai Lai, Hans Hsienhong Lin, Chen-Chung Chu, Li-Yu Wang |
Journal | Journal of gastroenterology and hepatology
(J Gastroenterol Hepatol)
Vol. 30
Issue 5
Pg. 891-9
(May 2015)
ISSN: 1440-1746 [Electronic] Australia |
PMID | 25389088
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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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
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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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