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.
OBJECTIVE
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.


CONCLUSIONS
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.
Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
Tzu-Wei
TW
Wu
Chuen-Fei
CF
Chen
Sheng-Kai
SK
Lai
Hans Hsienhong
HH
Lin
Chen-Chung
CC
Chu
Li-Yu
LY
Wang
D000293:Adolescent; D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D059868:HLA-DP beta-Chains / Q000235:genetics*; D006509:Hepatitis B / Q000276:immunology* / Q000517:prevention & control*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000235:genetics*; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D013997:Time Factors
D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D017325:Hepatitis B Vaccines
HLA-DP; adolescents; genome-wide association study; hepatitis B vaccination