title: Responses to booster hepatitis B vaccination are significantly correlated with genotypes of human leukocyte antigen (HLA)-DPB1 in neonatally vaccinated adolescents.
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.
authors.affiliation: Department of Medicine, Mackay Medical College, No. 46, Sec. 3, Jhong-Jheng Rd., San-Jhih Dist., New Taipei City, 252, Taiwan.
authors.forename: Tzu-Wei
authors.initials: TW
authors.lastname: Wu
authors.forename: Chen-Chung
authors.initials: CC
authors.lastname: Chu
authors.forename: Tzu-Ying
authors.initials: TY
authors.lastname: Ho
authors.forename: Huei-Wen
authors.initials: HW
authors.lastname: Chang Liao
authors.forename: Sheng-Kai
authors.initials: SK
authors.lastname: Lin
authors.forename: Marie
authors.initials: M
authors.lastname: Lin
authors.forename: Hans Hsienhong
authors.initials: HH
authors.lastname: Lin
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D005838:Genotype; D059868:HLA-DP beta-Chains / Q000235:genetics* / Q000378:metabolism; D006509:Hepatitis B / Q000517:prevention & control; D006510:Hepatitis B Antibodies / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D008297:Male; D016017:Odds Ratio; D012307:Risk Factors; D014611:Vaccination
chemical_list: D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines