Effects of vitamin A and D receptor gene polymorphisms/haplotypes on immune responses to measles vaccine.
Effects of vitamin A and D receptor gene polymorphisms/haplotypes on immune responses to measles vaccine.
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DOI：
10.1097/fpc.0b013e32834df186
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发表时间：
2012-01
影响因子：
2.6
通讯作者：
Poland GA
中科院分区：
文献类型：
--
作者：
Ovsyannikova IG;Haralambieva IH;Vierkant RA;O'Byrne MM;Jacobson RM;Poland GA
维生素 A 和 D 及其受体是免疫系统（包括疫苗免疫反应）的重要调节剂。我们评估了 745 名受试者接种两剂麻疹疫苗后维生素 A（RARA、RARB 和 RARG）和维生素 D 受体 (VDR)/RXRA 基因多态性与个体间免疫反应差异之间的关联。使用 tagSNP 方法，我们对 745 名健康儿童的维生素 A 和 D 受体基因的 391 个多态性进行了基因分型。在白种人中，RARB 单倍型 (rs6800566/rs6550976/rs9834818) 与麻疹抗体 (全局 p=0.013) 和细胞因子分泌水平的变化显着相关，例如白种人中的 IL-10 (全局 p=0.006)、IFN-α (全局 p=0.008) 和 TNF-α (全局 p=0.039)子组。具体而言，RARB 单倍型 AAC 与较高（t 统计量 3.27，p=0.001）的麻疹抗体水平相关。另一方面，rs6550978/rs6777544 的单倍型 GG 与白种人亚组中较低的抗体水平相关（t 统计量 -2.32，p=0.020）。在敏感性分析中，当 IL-10 分泌水平模型中包含单个 SNP rs12630816 时，RARB 单倍型 CTGGGCAA 仍保持轻微显着性 (p<0.02)。较低的麻疹特异性 IFN-γ Elispot 反应与单倍型 rs11102986/rs11103473/rs11103482/rs10776909/rs12004589/rs35780541/rs2266677/rs875444 之间存在显着相关性（全局 p=0.004）白种人 RXRA 基因中的 rs6537944/rs3118571（全局 p<0.001）。我们还发现多个 RARB、VDR 和 RXRA SNP/单倍型与麻疹特异性 IL-2、IL-6、IL-10、IFN-α、IFN-γ、IFNλ-1 和 TNF-α 细胞因子分泌之间的关联。我们的结果表明，维生素 A 和 D 受体基因中的特定等位基因变异和单倍型可能会影响对麻疹疫苗的适应性免疫反应。
Vitamin A and D, and their receptors, are important regulators of the immune system, including vaccine immune response. We assessed the association between polymorphisms in the vitamin A (RARA, RARB and RARG) and vitamin D receptor (VDR)/RXRA genes and inter-individual variations in immune responses after two doses of measles vaccine in 745 subjects. Using a tagSNP approach, we genotyped 745 healthy children for the 391 polymorphisms in vitamin A and D receptor genes. The RARB haplotype (rs6800566/rs6550976/rs9834818) was significantly associated with variations in both measles antibody (global p=0.013) and cytokine secretion levels, such as IL-10 (global p=0.006), IFN-α (global p=0.008), and TNF-α (global p=0.039) in the Caucasian subgroup. Specifically, the RARB haplotype AAC was associated with higher (t-statistic 3.27, p=0.001) measles antibody levels. At the other end of the spectrum, haplotype GG for rs6550978/rs6777544 was associated with lower antibody levels (t-statistic −2.32, p=0.020) in the Caucasian subgroup. In a sensitivity analysis, the RARB haplotype CTGGGCAA remained marginally significant (p<0.02) when the single SNP rs12630816 was included in the model for IL-10 secretion levels. A significant association was found between lower measles-specific IFN-γ Elispot responses and haplotypes rs11102986/rs11103473/rs11103482/rs10776909/rs12004589/rs35780541/rs2266677/rs875444 (global p=0.004) and rs6537944/rs3118571 (global p<0.001) in the RXRA gene for Caucasians. We also found associations between multiple RARB, VDR and RXRA SNPs/haplotypes and measles-specific IL-2, IL-6, IL-10, IFN-α, IFN-γ, IFNλ-1, and TNF-α cytokine secretion. Our results suggest that specific allelic variations and haplotypes in the vitamin A and D receptor genes may influence adaptive immune responses to measles vaccine.