Centre for Paediatric Epidemiology and Biostatistics and MRC Centre for the Epidemiology of Child Health, UCL Institute of Child Health, London, UK.
Allergy. 2012 Aug;67(8):1033-40. doi: 10.1111/j.1398-9995.2012.02856.x. Epub 2012 Jun 12.
The hormonal form of vitamin D affects both adaptive and innate immune functions involved in the development of allergies. Certain genotypes have been seen to alter the association between vitamin D deficiency (VDD) and the risk of food sensitization in children.
We examined 27 functional single nucleotide polymorphisms (SNPs) in/near selected candidate genes for association with total immunoglobulin E (IgE) and effect modification by 25-hydroxyvitamin D in the 1958 British birth cohort (aged 45 years, n = 4921). A cut-off value of 50 nmol/L was used to define VDD.
Four SNPs (in FCER1A, IL13, and CYP24A1) and three SNPs (in IL4 and CYP24A1) were associated with total IgE and specific IgE, respectively, after correction for multiple testing. As in a previous study, MS4A2 (rs512555, P(interaction) = 0.04) and IL4 (rs2243250, P(interaction) = 0.02), and their composite score (P(interaction) = 0.009) modified the association between VDD and allergy-related outcome. Vitamin D deficiency was associated with higher total IgE only in the carriers of the 'C' allele (IL4), which is present in 86% of white Europeans, while only 26% of Chinese and <20% of some African populations are carriers.
Our study on white European adults was consistent with a previous study on children from largely non-white ethnic groups, suggesting that IL4 and MS4A2 genotypes modify the association between VDD and allergy risk. The risk allele in IL4 is present in nearly 90% of white Europeans, while less than a quarter are carriers in some other populations, highlighting the need to consider possible ethnic differences in allergy-related responsiveness to VDD.
维生素 D 的激素形式影响过敏发展过程中涉及的适应性和固有免疫功能。某些基因型已被发现可改变维生素 D 缺乏（VDD）与儿童食物致敏风险之间的关联。
我们在 1958 年英国出生队列中（年龄 45 岁，n = 4921），检查了与总免疫球蛋白 E（IgE）相关的/附近的 27 个候选基因中的功能性单核苷酸多态性（SNP），以及 25-羟维生素 D 的效应修饰。使用 50 nmol/L 的截断值来定义 VDD。
在经过多次测试校正后，有 4 个 SNP（位于 FCER1A、IL13 和 CYP24A1 中）和 3 个 SNP（位于 IL4 和 CYP24A1 中）与总 IgE 和特异性 IgE 相关。与之前的研究一样，MS4A2（rs512555，P（交互）= 0.04）和 IL4（rs2243250，P（交互）= 0.02）及其复合评分（P（交互）= 0.009）也修饰了 VDD 与过敏相关结果之间的关联。只有在 IL4 的‘C’等位基因（在 86%的白种欧洲人中存在）携带者中，VDD 才与总 IgE 升高相关，而在中国人中只有 26%的携带者，而在一些非洲人群中则不到 20%的携带者。
我们对白人欧洲成年人的研究与之前对主要是非白人种族儿童的研究一致，表明 IL4 和 MS4A2 基因型修饰了 VDD 与过敏风险之间的关联。IL4 中的风险等位基因在近 90%的白种欧洲人中存在，而在其他一些人群中，不到四分之一的人是携带者，这突出表明需要考虑 VDD 与过敏相关反应的可能种族差异。
