Replication of rubella vaccine population genetic studies: Validation of HLA genotype and humoral response associations
Replication of rubella vaccine population genetic studies: Validation of HLA genotype and humoral response associations
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DOI：
10.1016/j.vaccine.2009.08.109
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发表时间：
2009-11-16
期刊：
影响因子：
5.5
通讯作者：
Poland, Gregory A.
中科院分区：
文献类型：
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作者：
Ovsyannikova, Inna G.;Jacobson, Robert M.;Poland, Gregory A.
在人口研究中发现的所谓的遗传关联需要验证才能得到证实。我们之前报道了346名年龄在12-18岁(第一组)的青少年在接种两剂风疹疫苗后产生的免疫反应和人类白细胞抗原相关性。我们试图通过在396名年龄在11-19岁(第二组)的新受试者中验证这些相关性，来复制在那项工作中发现的相关性，这些受试者都接种了两剂含有风疹的疫苗。我们发现，B*2705(第一队列中位数20.9IU/ml，p=0.028：第二队列20.5IU/ml，p=0.001)和DPA1*0201(第一队列中位数32.5IU/ml，p=0.048；第二队列25.8IU/ml，p=0.025)等位基因与风疹诱导的抗体水平一致。此外，DPB1*0401(第一队列中位数43.5IU/ml，p=0.021；第二队列36.2IU/ml，p=0.002)等位基因与两个人群中较高的抗体水平相关。DRB1*04-DQB1*03-DPB1*03(第1组平均25.2IU/ml，p=0.011；第2组21.4IU/ml，p=0.032)和DRB1*15/16-DQBI06-DPB1*03(第1组16.3IU/ml，p=0.043；第2组19.1IU/ml，p=0.023)单倍型与较低的风疹特异性抗体之间存在关联。这项研究为风疹疫苗诱导的体液反应与特定的I类和II类人类白细胞抗原标记物和单倍型之间的关联提供了确凿的证据，并进一步证明了它们对风疹免疫反应的影响。(C)2009爱思唯尔有限公司。保留所有权利。
Purported genetic associations found in population studies require validation for confirmation. We previously reported rubella vaccine-induced immune responses and HLA associations in 346 adolescents, age 12-18 years (1st cohort), following two doses of a rubella-containing vaccine. We sought to replicate the associations discovered in that work by verifying these associations in a new cohort of 396 subjects, age 11-19 years (2nd cohort), all having had two doses of a rubella-containing vaccine. We found that B*2705 (median 1st cohort 20.9 IU/ml, p =0.028: 2nd cohort 20.5 IU/ml, p =0.001) and DPA1*0201 (median 1st cohort 32.5 IU/ml, p=0.048; 2nd cohort 25.8 IU/ml, p =0.025) alleles were consistently associated with lower rubella-induced antibodies. Further, DPB1*0401 (median 1st cohort 43.5 IU/ml,p =0.021; 2nd cohort 36.2 IU/ml, p =0.002) alleles were associated with higher antibody levels in both populations. The association of DRB1*04-DQB1*03-DPB1*03 (mean 1st cohort 25.2 IU/ml, p =0.011; 2nd cohort 21.4 IU/ml, p =0.032) and DRB1*15/16-DQBI*06-DPB1*03 (1st cohort 16.3 IU/ml, p=0.043; 2nd cohort 19.1 IU/ml, p =0.023) haplotypes with lower rubella-specific antibodies was observed in both studies. This study provides confirmatory evidence for an association between specific class I and II HLA markers and haplotypes with rubella vaccine-induced humoral responses and lends further weight to their influence on rubella immune responses. (C) 2009 Elsevier Ltd. All rights reserved.