The Association of CD46, SLAM and CD209 Cellular Receptor Gene SNPs with Variations in Measles Vaccine-Induced Immune Responses: A Replication Study and Examination of Novel Polymorphisms
The Association of CD46, SLAM and CD209 Cellular Receptor Gene SNPs with Variations in Measles Vaccine-Induced Immune Responses: A Replication Study and Examination of Novel Polymorphisms
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DOI：
10.1159/000331585
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发表时间：
2011-01-01
期刊：
影响因子：
1.8
通讯作者：
Poland, Gregory A.
中科院分区：
文献类型：
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作者：
Ovsyannikova, Inna G.;Haralambieva, Iana H.;Poland, Gregory A.
背景：麻疹病毒 (MV) 与两种已知的细胞受体相互作用：CD46 和 SLAM。跨膜受体 CD209 与 MV 相互作用并增强树突状细胞感染。方法：作为一项更大规模研究的一部分，对先前接种过麻疹、腮腺炎、风疹疫苗的 764 名受试者进行了 CD46、SLAM 和 CD209 基因中 66 个候选 SNP 的基因分型。结果：先前检测到的 CD46 SNP rs2724384 与麻疹特异性抗体的关联在本研究中成功复制。内含子 CD46 SNP 的次要等位基因 G 的代表性增加与抗体水平的等位基因剂量相关降低（978 vs. 522 mIU/ml，p = 0.0007）相关。该多态性 rs2724384 还证明与 IL-6 (p = 0.02)、IFN-α (p = 0.007) 和 TNF-α (p = 0.0007) 反应相关。在我们之前的研究中，SLAM 基因中与麻疹抗体水平相关的两个多态性（编码 rs164288 和内含子 rs11265452）在本研究中分别与 IFN-gamma Elispot (p = 0.04) 和 IL-10 反应 (p = 0.0008) 相关。我们发现 CD46 基因和 TNF-α 分泌中的单倍型 AACGGAATGGAAAG (p = 0.009) 和 GGCCGAGAGGAGAG (p < 0.001) 之间存在关联。结论：了解这些遗传多态性对免疫反应变异的功能和机制影响可能有助于指导新的麻疹和潜在的其他病毒疫苗设计，并更好地了解麻疹免疫遗传学。版权所有 (C) 2011 S. Karger AG，巴塞尔
Background: The measles virus (MV) interacts with two known cellular receptors: CD46 and SLAM. The transmembrane receptor CD209 interacts with MV and augments dendritic cell infection. Methods: 764 subjects previously immunized with measles-mumps-rubella vaccine were geno-typed for 66 candidate SNPs in the CD46, SLAM and CD209 genes as part of a larger study. Results: A previously detected association of the CD46 SNP rs2724384 with measles-specific antibodies was successfully replicated in this study. Increased representation of the minor allele G for an intronic CD46 SNP was associated with an allele dose-related decrease (978 vs. 522 mIU/ml, p = 0.0007) in antibody levels. This polymorphism rs2724384 also demonstrated associations with IL-6 (p = 0.02), IFN-alpha (p = 0.007) and TNF-alpha (p = 0.0007) responses. Two polymorphisms (coding rs164288 and intronic rs11265452) in the SLAM gene that were associated with measles antibody levels in our previous study were associated with IFN-gamma Elispot (p = 0.04) and IL-10 responses (p = 0.0008), respectively, in this study. We found associations between haplotypes, AACGGAATGGAAAG (p = 0.009) and GGCCGAGAGGAGAG (p < 0.001), in the CD46 gene and TNF-alpha secretion. Conclusion: Understanding the functional and mechanistic consequences of these genetic polymorphisms on immune response variations could assist in directing new measles and potentially other viral vaccine design, and in better understanding measles immunogenetics. Copyright (C) 2011 S. Karger AG, Basel