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Responses to booster hepatitis B vaccination are significantly correlated with genotypes of human leukocyte antigen (HLA)-DPB1 in neonatally vaccinated adolescents

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Abstract

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) near the human leukocyte antigen (HLA)-DP loci that were significantly correlated with outcomes of hepatitis B virus (HBV) infection. We performed a case–control study nested in a well-characterized cohort of booster recipients to assess whether genetic variants of HLA-DPB1 are also associated with response to hepatitis B (HB) vaccination. The cases and controls were 171 and 510 booster recipients whose post-booster titers of antibodies against HBV surface antigen (anti-HBs) were undetectable and detectable, respectively. The HLA-DPB1 genotype was determined using sequence-based techniques. The frequencies of HLA-DPB1 alleles were significantly different between cases and controls (p = 1.7 × 10−8). The HLA-DPB1 05:01 and 09:01 alleles were significantly more frequent in the cases, and 02:01:02, 02:02, 03:01:01, 04:01:01, and 14:01, were significantly more frequent in the controls. The adjusted odds ratio (OR) of undetectable post-booster anti-HBs titers was significantly correlated with the number of risk alleles (p for trend = 3.8 × 10−5). For the number of protective alleles, the trend was significantly inversed (p for trend = 1.3 × 10−5). As compared with subjects with two risk alleles, adjusted OR were 0.34 (95 % confidence interval [CI] 0.21–0.55) and 0.20 (95 % CI 0.08–0.48) for subjects with 1 and 2 protective alleles, respectively. The HLA-DPB1 02:02, 04:01:01, 05:01 and 09:01 alleles were also significantly correlated with the likelihoods of undetectable pre-booster anti-HBs titers. Our results indicated that HLA-DPB1 is significantly correlated with response to booster HB vaccination in adolescent who had received postnatal active HB vaccination. HLA-DBP1 may also determine the long-term persistence of response to HB vaccination.

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Abbreviations

Anti-HBs:

Antibodies to hepatitis B surface antigen

Anti-HBc:

Antibodies to hepatitis B core antigen

CI:

Confidence interval

HB:

Hepatitis B

HBIG:

Hepatitis B immunoglobin

HBeAg:

Hepatitis B e antigen

HBsAg:

Hepatitis B surface antigen

HBV:

Hepatitis B virus

HLA:

Human leukocyte antigens

OR:

Odds ratio

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Acknowledgments

We thank to the staffs of the senior high schools and health stations in Hualien County and the Center of Disease Control, Department of Health, Taiwan, for their valuable contribution. This research was supported by grants from Mackay Medical College (981B03 & 991A01) and the National Science Council, Taiwan (NSC97-2314-B-715-001-MY3). The funding agencies played no role in the work.

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Authors and Affiliations

  1. Department of Medicine, Mackay Medical College, No. 46, Sec. 3, Jhong-Jheng Rd., San-Jhih Dist., New Taipei City, 252, Taiwan

    Tzu-Wei Wu & Li-Yu Wang

  2. Transfusion Medicine Laboratory, Medical Research Department, Mackay Memorial Hospital, Taipei City, Taiwan

    Chen-Chung Chu & Marie Lin

  3. Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taiwan

    Chen-Chung Chu

  4. Institute of Public Health, Tzu Chi University, Hualien, Taiwan

    Tzu-Ying Ho, Huei-Wen Chang Liao, Sheng-Kai Lin & Li-Yu Wang

  5. Department of Gastroenterology, Buddhist Tzu Chi General Hospital Taipei Branch, No. 289 Jianguo Rd., Xindian Dist., New Taipei City, 231, Taiwan

    Hans Hsienhong Lin

  6. Department of Internal Medicine School of Medicine, Tzu Chi University, Hualien, Taiwan

    Hans Hsienhong Lin

  7. Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan

    Li-Yu Wang

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  1. Tzu-Wei Wu
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  2. Chen-Chung Chu
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  5. Sheng-Kai Lin
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  7. Hans Hsienhong Lin
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Correspondence to Hans Hsienhong Lin or Li-Yu Wang.

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T.-W. Wu and C.-C. Chu contributed equally to this work.

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Wu, TW., Chu, CC., Ho, TY. et al. Responses to booster hepatitis B vaccination are significantly correlated with genotypes of human leukocyte antigen (HLA)-DPB1 in neonatally vaccinated adolescents. Hum Genet 132, 1131–1139 (2013). https://doi.org/10.1007/s00439-013-1320-5

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