Associations between single nucleotide polymorphisms and haplotypes in cytokine and cytokine receptor genes and immunity to measles vaccination.
Associations between single nucleotide polymorphisms and haplotypes in cytokine and cytokine receptor genes and immunity to measles vaccination.
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DOI：
10.1016/j.vaccine.2011.08.083
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发表时间：
2011-10-19
期刊：
影响因子：
5.5
通讯作者：
Poland, Gregory A.
中科院分区：
文献类型：
--
作者：
Haralambieva, Iana H.;Ovsyannikova, Inna G.;Kennedy, Richard B.;Vierkant, Robert A.;Pankratz, V. Shane;Jacobson, Robert M.;Poland, Gregory A.
鉴定麻疹疫苗诱导免疫的宿主遗传决定因素可用于设计更好的疫苗，并最终预测对疫苗接种的免疫应答。我们在两剂MMR疫苗后的745名学龄儿童的种族多样性队列中，对56种细胞因子/细胞因子受体基因的801个遗传标记进行了全面的候选基因关联研究。使用线性回归方法，我们研究了SNPs/单倍型和麻疹病毒特异性免疫力之间的关联。48个显著的SNP与中和抗体和麻疹特异性IFNγ Elispot应答的变化相关（p<0.05）。我们的研究重复了先前发现的功能性IL 12 B遗传变异rs3212227与麻疹特异性体液免疫变异的重要关联（p=0.037）。同样，先前报道的两个启动子IL 10和IL 2多态性（rs 1800890和rs 2069762）与高加索人麻疹特异性细胞免疫相关（p≤0.034）。在白种人中，多种IL 7 R多态性，包括非同义功能SNP（rs6897932/Thr 244 Ile），与体液（p≤0.024）和/或细胞（IFNγ Elispot，p≤0.023）麻疹特异性免疫应答相关，但与非洲裔美国人无关。单倍型水平分析证实了IL 7 R遗传变异与高加索人群麻疹疫苗诱导的免疫力相关（总体p值=0.003）。我们的研究结果验证了以前的研究结果，并确定了新的合理的遗传决定因素，包括IL 7 R多态性，以种族特异性方式调节麻疹疫苗诱导的免疫力。
Identification of host genetic determinants of measles vaccine-induced immunity can be used to design better vaccines and ultimately predict immune responses to vaccination. We performed a comprehensive candidate gene association study across 801 genetic markers in 56 cytokine/cytokine receptor genes, in a racially diverse cohort of 745 schoolchildren after two doses of MMR vaccine. Using linear regression methodologies we examined associations between SNPs/haplotypes and measles virus-specific immunity. Forty-eight significant SNP associations with variations in neutralizing antibodies and measles-specific IFNγ Elispot responses were identified (p<0.05). Our study replicated an important previously found association of a functional IL12B genetic variant rs3212227 with variations in measles-specific humoral immunity (p=0.037). Similarly, two previously reported promoter IL10 and IL2 polymorphisms (rs1800890 and rs2069762) demonstrated associations with measles-specific cellular immunity in Caucasians (p≤0.034). Multiple IL7R polymorphisms, including a non-synonymous functional SNP (rs6897932/Thr244Ile), were associated with humoral (p≤0.024) and/or cellular (IFNγ Elispot, p≤0.023) measles-specific immune responses in Caucasians, but not African-Americans. Haplotype level analysis confirmed the association of IL7R genetic variants with measles vaccine-induced immunity in the Caucasian group (global p-value=0.003). Our results validate previous findings and identify new plausible genetic determinants, including IL7R polymorphisms, regulating measles vaccine-induced immunity in a race-specific manner.
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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：
5.5
作者：
Klein, Nicola P.;Holmes, Tyson H.;Dekker, Cornelia L.
通讯作者：
Dekker, Cornelia L.
影响因子：
--
作者：
Dhiman, N.;Ovsyannikova, G.;Poland, G. A.
通讯作者：
Poland, G. A.
影响因子：
5.5
作者：
Baynam, Gareth;Zhang, Guicheng;Le Souef, Peter N.
通讯作者：
Le Souef, Peter N.
影响因子：
30.8
作者：
Lundmark, Frida;Duvefelt, Kristina;Hillert, Jan
通讯作者：
Hillert, Jan