Associations between SNPs in candidate immune-relevant genes and rubella antibody levels: a multigenic assessment.
Associations between SNPs in candidate immune-relevant genes and rubella antibody levels: a multigenic assessment.
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DOI：
10.1186/1471-2172-11-48
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发表时间：
2010-10-05
期刊：
影响因子：
3
通讯作者：
Poland GA
中科院分区：
文献类型：
--
作者：
Pankratz VS;Vierkant RA;O'Byrne MM;Ovsyannikova IG;Poland GA
免疫反应的机制是在一个高度复杂的调控系统中构建的。与风疹疫苗免疫反应变异的遗传关联通常是一次评估一个位点。我们同时评估了标记84个候选免疫反应基因的726个snp与风疹特异性抗体水平之间的关系。从接种了两剂MMR疫苗的714名学龄儿童中获得了血液样本。风疹特异性抗体水平与726个候选标签SNP之间的关系在各种多基因分析中一次评估一个SNP。单snp评估鉴定出4个snp似乎与风疹抗体水平单一相关：LTA基因5'UTR中的rs2844482 （p = 0.0002）和rs2857708 (p = 0.001)， IL6基因5'UTR中的rs7801617 (p = 0.0005)， IL4R基因5'UTR中的rs4787947 （p = 0.002）。虽然没有明显的证据表明候选snp之间存在显性遗传关联，但多基因分析确定了29个snp与风疹抗体水平显著相关（p = 0.017）。这组snp不仅包括那些单因素显著的snp，还包括那些如果单独考虑其他snp就无法识别的snp。首次对候选snp和风疹抗体水平之间的关联进行多基因评估，确定了大量的遗传关联，这些关联在单一因素下并不重要。为了更好地理解疫苗接种反应的全部遗传复杂性，重要的是要考虑像这里应用的方法。
The mechanisms of immune response are structured within a highly complex regulatory system. Genetic associations with variation in the immune response to rubella vaccine have typically been assessed one locus at a time. We simultaneously assessed the associations between 726 SNPs tagging 84 candidate immune response genes and rubella-specific antibody levels. Blood samples were obtained from 714 school-aged children who had received two doses of MMR vaccine. Associations between rubella-specific antibody levels and 726 candidate tagSNPs were assessed both one SNP at a time and in a variety of multigenic analyses. Single-SNP assessments identified 4 SNPs that appeared to be univariately associated with rubella antibody levels: rs2844482 (p = 0.0002) and rs2857708 (p = 0.001) in the 5'UTR of the LTA gene, rs7801617 in the 5'UTR of the IL6 gene (p = 0.0005), and rs4787947 in the 5'UTR of the IL4R gene (p = 0.002). While there was not significant evidence in favor of epistatic genetic associations among the candidate SNPs, multigenic analyses identified 29 SNPs significantly associated with rubella antibody levels when selected as a group (p = 0.017). This collection of SNPs included not only those that were significant univariately, but others that would not have been identified if only considered in isolation from the other SNPs. For the first time, multigenic assessment of associations between candidate SNPs and rubella antibody levels identified a broad number of genetic associations that would not have been deemed important univariately. It is important to consider approaches like those applied here in order to better understand the full genetic complexity of response to vaccination.
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影响因子：
3.2
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.
通讯作者：
Poland, Gregory A.
影响因子：
2.7
作者：
Ovsyannikova, IG;Jacobson, RM;Poland, GA
通讯作者：
Poland, GA
影响因子：
--
作者：
Dhiman, N.;Ovsyannikova, G.;Poland, G. A.
通讯作者：
Poland, G. A.
影响因子：
56.9
作者：
Liu, PT;Stenger, S;Modlin, RL
通讯作者：
Modlin, RL
影响因子：
2.7
作者：
Kennedy, Richard B.;Ovsyannikova, Inna G.;Poland, Gregory A.
通讯作者：
Poland, Gregory A.