Polymorphisms in the Vitamin A Receptor and Innate Immunity Genes Influence the Antibody Response to Rubella Vaccination
Polymorphisms in the Vitamin A Receptor and Innate Immunity Genes Influence the Antibody Response to Rubella Vaccination
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DOI：
10.1086/649588
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发表时间：
2010-01-15
影响因子：
6.4
通讯作者：
Poland, Gregory A.
中科院分区：
文献类型：
--
作者：
Ovsyannikova, Inna G.;Haralambieva, Iana H.;Poland, Gregory A.
背景遗传多态性在风疹疫苗诱导的免疫中起重要作用。我们对714名健康儿童在接种了2剂与年龄相适应的风疹疫苗后进行了142个潜在单核苷酸多态性（SNP）的基因分型。在维生素A受体，视黄酸诱导基因I（RIG-I），和三方基序5和22（TRIM 5和TRIM 22）基因的特异性多态性与风疹疫苗的体液免疫显着相关。维生素A受体基因中rs 4416353的次要等位基因与风疹抗体应答的等位基因剂量相关性降低（P= 0.019）相关。维生素A受体基因中rs6793694的次要等位基因与等位基因剂量相关抗体降低相关（P= 0.039）。RIG-I基因中非同义SNP rs 10813831（Arg 7 Cys）的微小变异与风疹抗体水平从37.4 IU/mL至28.0 IU/mL的等位基因剂量相关性降低相关（P= 0.035），而5 'UTR SNP的次要等位基因的代表性增加，抗逆转录病毒TRIM 5基因中的rs3824949（P=.015）与风疹抗体等位基因剂量相关性增加相关。特别令人感兴趣的是，TRIM 5基因中的非同义SNP rs3740996（His 43 Tyr）与风疹抗体应答的变化相关（P= 0.016），此前已发现其发挥重要的功能作用。这些发现进一步扩展了我们对风疹疫苗诱导免疫机制的免疫遗传学理解。
Background. Genetic polymorphisms play an important role in rubella vaccine-induced immunity.Methods. We genotyped 714 healthy children after 2 age-appropriate doses of rubella-containing vaccine for 142 potential single-nucleotide polymorphisms (SNPs).Results. Specific polymorphisms in the vitamin A receptor, retinoic acid-inducible gene I (RIG-I), and tripartite motif 5 and 22 (TRIM5 and TRIM22) genes were significantly associated with rubella vaccine humoral immunity. The minor allele of the rs4416353 in the vitamin A receptor gene was associated with an allele dose-related decrease (P=.019) in rubella antibody response. The minor allele of rs6793694, in the vitamin A receptor gene, was associated with an allele dose-related antibody decrease (P=.039). The minor variant of nonsynonymous SNP rs10813831 (Arg7Cys) in the RIG-I gene was associated with an allele dose-related decrease in rubella antibody level from 37.4 to 28.0 IU/mL (P=.035), whereas increased representation of the minor allele of the 5'UTR SNP (rs3824949, P=.015) in the antiretroviral TRIM5 gene was associated with an allele dose-related increase in rubella antibody. It is of particular interest that the nonsynonymous SNP rs3740996 (His43Tyr) in the TRIM5 gene was associated with variations in rubella antibody response (P=.016) after having been previously found to play a significant functional role.Conclusions. These findings further expand our immunogenetic understanding of mechanisms of rubella vaccine-induced immunity.