SNP/haplotype associations in cytokine and cytokine receptor genes and immunity to rubella vaccine.
SNP/haplotype associations in cytokine and cytokine receptor genes and immunity to rubella vaccine.
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DOI：
10.1007/s00251-010-0423-6
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发表时间：
2010-04
期刊：
影响因子：
3.2
通讯作者：
Poland, Gregory A.
中科院分区：
文献类型：
--
作者：
Dhiman, Neelam;Haralambieva, Iana H.;Kennedy, Richard B.;Vierkant, Robert A.;O'Byrne, Megan M.;Ovsyannikova, Inna G.;Jacobson, Robert M.;Poland, Gregory A.
对疫苗接种的有效免疫反应部分是调节细胞因子网络的多个基因等位基因的复杂相互作用。我们对健康儿童（n=738，11-19 岁）的 Th1/Th2/炎症细胞因子/细胞因子受体进行了基因分型研究，以确定个体单核苷酸多态性 (SNP)/单倍型与接种两剂风疹疫苗后免疫结果之间的关联。使用 ldSelect 方法选择 SNP (n=501)，并使用 Illumina GoldenGate™ 和 TaqMan 检测进行基因分型。通过免疫测定法测量风疹 IgG 水平，并通过 ELISA 测量分泌的细胞因子。线性回归和事后单倍型分析用于确定单个 SNP/单倍型与免疫结果之间的关联。 TNFA 基因启动子 SNP（rs2844482 和 rs2857708）的次要等位基因携带量的增加与风疹抗体的剂量相关增加有关。 IL-6 分泌与 TNFRSF1B 基因中的 5 个内含子 SNP 以等位基因剂量相关的方式同向相关（p≤0.01），而 IL12B 基因中的 5 个启动子/内含子 SNP 与 IL-6 分泌的变化相关。 TNFA 单倍型 AAACGGGGC (t 统计量 = 3.32) 和 IL12B 启动子单倍型 TAG (t 统计量 = 2.66) 分别与较高水平 (p≤0.01) 风疹 IgG 和 IL-6 分泌相关。我们鉴定了 TNFA/TNFRSF1B 和 IL12B 基因中的单个 SNP/单倍型，它们似乎调节风疹疫苗接种的免疫力。识别此类“基因指纹”可以预测疫苗反应的结果并为新的疫苗策略提供信息。
An effective immune response to vaccination is, in part, a complex interaction of alleles of multiple genes regulating cytokine networks. We conducted a genotyping study of Th1/Th2/inflammatory cytokines/cytokine receptors in healthy children (n=738, 11–19 years) to determine associations between individual single-nucleotide polymorphisms (SNPs)/haplotypes and immune outcomes after two doses of rubella vaccine. SNPs (n=501) were selected using the ldSelect-approach and genotyped using Illumina GoldenGate™ and TaqMan assays. Rubella-IgG levels were measured by immunoassay and secreted cytokines by ELISA. Linear regression and post hoc haplotype analyses were used to determine associations between single SNPs/haplotypes and immune outcomes. Increased carriage of minor alleles for the promoter SNPs (rs2844482 and rs2857708) of the TNFA gene were associated with dose-related increases in rubella antibodies. IL-6 secretion was co-directionally associated (p≤0.01) with five intronic SNPs in the TNFRSF1B gene in an allele dose-related manner, while five promoter/intronic SNPs in the IL12B gene were associated with variations in IL-6 secretion. TNFA haplotype AAACGGGGC (t-statistic=3.32) and IL12B promoter haplotype TAG (t-statistic=2.66) were associated with higher levels of (p≤0.01) rubella-IgG and IL-6 secretion, respectively. We identified individual SNPs/haplotypes in TNFA/TNFRSF1B and IL12B genes that appear to modulate immunity to rubella vaccination. Identification of such “genetic fingerprints” may predict the outcome of vaccine response and inform new vaccine strategies.
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