2'-5'-Oligoadenylate synthetase single-nucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine.
2'-5'-Oligoadenylate synthetase single-nucleotide polymorphisms and haplotypes are associated with variations in immune responses to rubella vaccine.
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DOI：
10.1016/j.humimm.2010.01.004
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发表时间：
2010-04
期刊：
影响因子：
2.7
通讯作者：
Poland, Gregory A.
中科院分区：
文献类型：
--
作者：
Haralambieva, Iana H.;Dhiman, Neelam;Ovsyannikova, Inna G.;Vierkant, Robert A.;Pankratz, V. Shane;Jacobson, Robert M.;Poland, Gregory A.
关键词：
干扰素诱导的抗病毒基因是先天性抗病毒防御的重要参与者，也是免疫应答异质性的潜在决定因素。我们选择了114个候选单核苷酸多态性（SNPs）从12个抗病毒基因使用LD tagSNP选择方法和基因分型他们在一个队列的738名学童接种两剂风疹疫苗。SNPs/单倍型和风疹病毒特异性免疫措施之间的关联进行了评估，使用线性回归方法。我们确定了23个在2′-5′-寡腺苷酸合成酶（OAS）基因簇内的多态性与风疹病毒特异性IL-2、IL-10、IL-6分泌和抗体水平之间的显著关联（p < 0.05）。3个OAS 1 SNP（rs3741981/Ser 162 Gly、rs 1051042/Thr 361 Arg、rs 2660）的次要等位基因变异位于功能重要性连锁不平衡区，与风疹病毒特异性IL-2/Th 1应答增加显著相关（p ≤ 0.024）。7个OAS 1和OAS 3启动子/调节SNP与IL-2分泌相似。重要的是，两个SNP（rs3741981和rs 10774670）独立地交叉调节风疹病毒特异性IL-10分泌水平（p ≤ 0.031）。此外，全球测试和个人单倍型分析显示OAS 1单倍型和风疹病毒特异性细胞因子分泌之间的显着关联。我们的研究结果表明，先天免疫和OAS基因变异可能参与调节风疹减毒活疫苗的适应性免疫应答的幅度和质量。
Interferon-induced antiviral genes are crucial players in innate antiviral defense and potential determinants of immune response heterogeneity. We selected 114 candidate single-nucleotide polymorphisms (SNPs) from 12 antiviral genes using an LD tagSNP selection approach and genotyped them in a cohort of 738 school children immunized with two doses of rubella vaccine. Associations between SNPs/haplotypes and rubella virus-specific immune measures were assessed using linear regression methodologies. We identified 23 significant associations (p < 0.05) between polymorphisms within the 2′-5′-oligoadenylate synthetase (OAS) gene cluster, and rubella virus-specific IL-2, IL-10, IL-6 secretion, and antibody levels. The minor allele variants of three OAS1 SNPs (rs3741981/Ser162Gly, rs1051042/Thr361Arg, rs2660), located in a linkage disequilibrium block of functional importance, were significantly associated with an increase in rubella virus-specific IL-2/Th1 response (p ≤ 0.024). Seven OAS1 and OAS3 promoter/regulatory SNPs were similarly associated with IL-2 secretion. Importantly, two SNPs (rs3741981 and rs10774670) independently cross-regulated rubella virus-specific IL-10 secretion levels (p ≤ 0.031). Furthermore, both global tests and individual haplotype analyses revealed significant associations between OAS1 haplotypes and rubella virus-specific cytokine secretion. Our results suggest that innate immunity and OAS genetic variations are likely involved in modulating the magnitude and quality of the adaptive immune responses to live attenuated rubella vaccine.
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影响因子：
--
作者：
Dhiman, N.;Ovsyannikova, G.;Poland, G. A.
通讯作者：
Poland, G. A.
抗病毒 2′,5′-寡腺苷酸合成酶（2′5′AS）酶活性的变化受 OAS1 基因中剪接接受位点单核苷酸多态性的控制
影响因子：
9.8
作者：
Bonnevie-Nielsen, V;Field, LL;Pociot, F
通讯作者：
Pociot, F
影响因子：
5.5
作者：
Dhiman, Neelam;Ovsyannikova, Inna G.;Poland, Gregory A.
通讯作者：
Poland, Gregory A.
DOI：
10.1016/j.bbrc.2005.02.101
发表时间：
2005-04-22
影响因子：
3.1
作者：
Hamano, E;Hijikata, M;Keicho, N
通讯作者：
Keicho, N
影响因子：
6.7
作者：
Poland, G. A.;Ovsyannikova, I. G.;Smith, D. I.
通讯作者：
Smith, D. I.