Variations in measles vaccine-specific humoral immunity by polymorphisms in SLAM and CD46 measles virus receptors
Variations in measles vaccine-specific humoral immunity by polymorphisms in SLAM and CD46 measles virus receptors
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DOI：
10.1016/j.jaci.2007.04.036
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发表时间：
2007-09-01
影响因子：
14.2
通讯作者：
Pankratz, V. Shane
中科院分区：
文献类型：
--
作者：
Dhiman, Neelam;Poland, Gregory A.;Pankratz, V. Shane
背景：麻疹感染需要 2 种细胞受体，即信号淋巴细胞激活分子 (SLAM) 和 CD46。 SLAM 和 CD46 基因中已知的新型单核苷酸多态性 (SNP) 可能会影响对麻疹疫苗的免疫反应。 目的：我们试图鉴定 SLAM 和 CD46 基因中的 SNP 与麻疹抗体反应变异之间的关联。 方法：我们对 339 名接种了 2 剂麻疹-腮腺炎-风疹疫苗的受试者的 SLAM 和 CD46 基因中已知的 SNP 进行了基因分型。我们还对 SLAM 和 CD46 的麻疹病毒结合域进行了测序，以鉴定新的 SNP。 结果：SLAM 基因中 rs3796504 和 rs164288 的次要等位基因的增加与麻疹特异性抗体中等位基因剂量相关的减少（4 倍）相关。与野生型 TT 相比，位于 SLAM 基因麻疹病毒结合域上游 33 bp 的非翻译区 rs12076998 的杂合基因型 TC 与较高的中位抗体水平相关（1991 vs 1467 IU/L，P =.01）。在 CD46 基因中，内含子 SNP (rs11118580) 的次要等位基因 C 与等位基因剂量相关的麻疹抗体下降相关（1072 与 1795 IU/L，P
Background: Measles infection requires 2 cellular receptors, signaling lymphocyte activation molecule (SLAM) and CD46. Known and novel single nucleotide polymorphisms (SNPs) in SLAM and CD46 genes might influence the immune response to measles vaccine.Objective: We sought to identify SNP associations in SLAM and CD46 genes with variations in measles antibody response.Methods: We genotyped known SNPs in SLAM and CD46 genes in 339 subjects vaccinated with 2 doses of measles-mumps-rubella vaccine. We also sequenced the measles virus-binding domains of SLAM and CD46 to identify novel SNPs.Results: Increased representation of minor alleles for rs3796504 and rs164288 in the SLAM gene was associated with an allele dose-related decrease (4-fold) in measles-specific antibodies. Heterozygous genotype TC for rs12076998 located in the untranslated region 33 bp upstream of the measles virus-binding domain of the SLAM gene was associated with higher median antibody levels (1991 vs 1467 IU/L, P =.01) compared with wild-type TT. Within the CD46 gene, the minor allele C for intronic SNP (rs11118580) was associated with an allele dose-related decrease in measles antibodies (1072 vs 1795 IU/L, P