BACKGROUND Although epigenetic mechanisms are important risk factors for allergic disease, few studies have evaluated DNA methylation differences associated with atopic dermatitis (AD), and none has focused on AD with eczema herpeticum (ADEH+). We will determine how methylation varies in AD individuals with/without EH and associated traits. We modeled differences in genome-wide DNA methylation in whole blood cells from 90 ADEH+, 83 ADEH-, and 84 non-atopic, healthy control subjects, replicating in 36 ADEH+, 53 ADEH-, and 55 non-atopic healthy control subjects. We adjusted for cell-type composition in our models and used genome-wide and candidate-gene approaches. RESULTS We replicated one CpG which was significantly differentially methylated by severity, with suggestive replication at four others showing differential methylation by phenotype or severity. Not adjusting for eosinophil content, we identified 490 significantly differentially methylated CpGs (ADEH+ vs healthy controls, genome-wide). Many of these associated with severity measures, especially eosinophil count (431/490 sites). CONCLUSIONS We identified a CpG in IL4 associated with serum tIgE levels, supporting a role for Th2 immune mediating mechanisms in AD. Changes in eosinophil level, a measure of disease severity, are associated with methylation changes, providing a potential mechanism for phenotypic changes in immune response-related traits.

中文翻译：

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与疱疹，湿疹和过敏反应相关的复制的甲基化变化。

背景技术尽管表观遗传机制是变应性疾病的重要危险因素，但很少有研究评估与特应性皮炎（AD）相关的DNA甲基化差异，并且还没有研究集中在疱疹性疱疹（ADEH +）的AD上。我们将确定在具有/不具有EH和相关性状的AD个体中，甲基化如何变化。我们对来自90个ADEH +，83个ADEH-和84个非过敏性健康对照受试者的全血细胞中全基因组DNA甲基化的差异进行建模，并在36个ADEH +，53个ADEH-和55个非过敏性健康对照受试者中复制。我们对模型中的细胞类型组成进行了调整，并使用了全基因组和候选基因方法。结果我们复制了一种CpG，该CpG的严重程度差异显着，在其他四个提示复制，表现出不同的甲基化表型或严重程度。在不调整嗜酸性粒细胞含量的情况下，我们确定了490个差异显着的甲基化CpG（ADEH +与健康对照，全基因组）。其中许多与严重性测量有关，尤其是嗜酸性粒细胞计数（431/490个位点）。结论我们确定了IL4中的CpG与血清tIgE水平相关，支持了AD中Th2免疫介导机制的作用。嗜酸性粒细胞水平的变化（一种衡量疾病严重程度的指标）与甲基化变化相关，为免疫应答相关性状的表型变化提供了潜在的机制。其中许多与严重性测量有关，尤其是嗜酸性粒细胞计数（431/490个位点）。结论我们确定了IL4中的CpG与血清tIgE水平相关，支持了AD中Th2免疫介导机制的作用。嗜酸性粒细胞水平的变化（一种衡量疾病严重程度的指标）与甲基化变化相关，为免疫应答相关性状的表型变化提供了潜在的机制。其中许多与严重性测量有关，尤其是嗜酸性粒细胞计数（431/490个位点）。结论我们确定了IL4中的CpG与血清tIgE水平相关，支持了AD中Th2免疫介导机制的作用。嗜酸性粒细胞水平的变化（一种衡量疾病严重程度的指标）与甲基化变化相关，为免疫应答相关性状的表型变化提供了潜在的机制。