Rubella vaccine-induced cellular immunity: evidence of associations with polymorphisms in the Toll-like, vitamin A and D receptors, and innate immune response genes.
Rubella vaccine-induced cellular immunity: evidence of associations with polymorphisms in the Toll-like, vitamin A and D receptors, and innate immune response genes.
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DOI：
10.1007/s00439-009-0763-1
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发表时间：
2010-02
期刊：
影响因子：
5.3
通讯作者：
Poland GA
中科院分区：
文献类型：
--
作者：
Ovsyannikova IG;Dhiman N;Haralambieva IH;Vierkant RA;O'Byrne MM;Jacobson RM;Poland GA
Toll 样、维生素 A 和 D 受体以及其他先天蛋白参与各种免疫功能。我们确定先天基因序列变异是否与风疹疫苗诱导的细胞因子免疫反应有关。我们对接种两剂风疹疫苗后的 714 名健康儿童（11-19 岁）进行了 148 个候选 SNP 标记的基因分型。通过 ELISA 测定风疹病毒诱导的细胞因子。在维生素 A 受体家族（RARA、RARB、TOP2B 和 RARG）、维生素 D 受体和维生素 D 信号传导下游介质 (RXRA) 基因中的 SNP 与风疹病毒特异性（IFN-γ、IL-2、IL-10、TNF-α 和 GM-CSF）细胞因子免疫反应之间发现了 22 个显着关联（P 值范围为 0.002–0.048）。 TLR3 基因启动子区 SNP（rs5743305，-8441A > T）与风疹特异性 GM-CSF 分泌相关。重要的是，TRIM5 基因编码区 rs3740996 (His43Tyr) 和 rs10838525 (Gln136Arg) 中的 SNP 分别与风疹病毒特异性 TNF-α 和 IL-2/GM-CSF 的等位基因剂量相关分泌相关，并且先前已被证明对抗病毒活性和 HIV-1 感染易感性具有功能性影响。我们确定了 RIG-I (DDX58) 基因中或涉及 RIG-I (DDX58) 基因和风疹特异性 TNF-α 分泌的单个 SNP 和单倍型之间的关联。这是第一篇提出证据的论文，证明 TLR、维生素 A、维生素 D 受体和先天免疫基因的多态性可以影响对风疹疫苗接种的适应性细胞因子反应。
Toll-like, vitamin A and D receptors and other innate proteins participate in various immune functions. We determined whether innate gene-sequence variations are associated with rubella vaccine-induced cytokine immune responses. We genotyped 714 healthy children (11–19 years of age) after two doses of rubella-containing vaccine for 148 candidate SNP markers. Rubella virus-induced cytokines were measured by ELISA. Twenty-two significant associations (range of P values 0.002–0.048) were found between SNPs in the vitamin A receptor family (RARA, RARB, TOP2B and RARG), vitamin D receptor and downstream mediator of vitamin D signaling (RXRA) genes and rubella virus-specific (IFN-γ, IL-2, IL-10, TNF-α, and GM-CSF) cytokine immune responses. A TLR3 gene promoter region SNP (rs5743305, −8441A > T) was associated with rubella-specific GM-CSF secretion. Importantly, SNPs in the TRIM5 gene coding regions, rs3740996 (His43Tyr) and rs10838525 (Gln136Arg), were associated with an allele dose-related secretion of rubella virus-specific TNF-α and IL-2/GM-CSF, respectively, and have been previously shown to have functional consequences regarding the antiviral activity and susceptibility to HIV-1 infection. We identified associations between individual SNPs and haplotypes in, or involving, the RIG-I (DDX58) gene and rubella-specific TNF-α secretion. This is the first paper to present evidence that polymorphisms in the TLR, vitamin A, vitamin D receptor, and innate immunity genes can influence adaptive cytokine responses to rubella vaccination.
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影响因子：
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作者：
Dhiman, N.;Ovsyannikova, G.;Poland, G. A.
通讯作者：
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