Responses to booster hepatitis B vaccination are significantly correlated with genotypes of human leukocyte antigen (HLA)-DPB1 in neonatally vaccinated adolescents
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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DOI：
10.1007/s00439-013-1320-5
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发表时间：
2013-10-01
期刊：
影响因子：
5.3
通讯作者：
Wang, Li-Yu
中科院分区：
文献类型：
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作者：
Wu, Tzu-Wei;Chu, Chen-Chung;Wang, Li-Yu
全基因组关联研究发现，人类白细胞抗原(HL A)-DP基因座附近的单核苷酸多态(SNPs)与乙肝病毒(HBV)感染的结局显著相关。我们进行了一项病例对照研究，嵌套在一组特征良好的加强免疫受者队列中，以评估人类白细胞抗原-DPB1的基因变异是否也与接种乙肝疫苗的反应有关。病例组和对照组分别为171例和510例加强免疫后抗-HBs抗体滴度未检出和未检出的受者。用基于序列的技术确定人类白细胞抗原-DPB1基因。HLADPB1等位基因频率在病例组和对照组之间差异有统计学意义(p=1.7×10(-8))。HLADPB1 05：01和09：01等位基因在病例组明显增多，02：01：02、02：02、03：01：01、04：01：01和14：01等位基因在对照组显著增多。调整后的优势比(OR)无法检测到加强免疫后抗-HBs滴度与危险等位基因的数量显著相关(趋势p=3.8×10(-5))。对于保护性等位基因的数量，趋势显著相反(趋势的p=1.3×10(-5))。与具有两个危险等位基因的受试者比较，具有1个和2个保护等位基因的受试者调整后的OR值分别为0.34(95%可信区间0.21~0.55)和0.20(95%CI 0.08~0.48)。HLADPB1 02：02、04：01：01、05：01和09：01等位基因与检测不到前加强免疫抗体滴度的可能性显著相关。我们的结果表明，在接受出生后主动接种乙肝疫苗的青少年中，人类白细胞抗原DPB1与加强免疫应答显著相关。HLA-DBP1还可能决定对乙肝疫苗免疫应答的长期持久性。
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 x 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 x 10(-5)). For the number of protective alleles, the trend was significantly inversed (p for trend = 1.3 x 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.