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首页> 外文期刊>Allergy >DNA methylation and allergic sensitizations: A genome-scale longitudinal study during adolescence
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DNA methylation and allergic sensitizations: A genome-scale longitudinal study during adolescence

机译：DNA甲基化和过敏性敏化：青春期期间的基因组纵向研究

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Background The presence of allergic sensitization has a major influence on the development and course of common childhood conditions such as asthma and rhinitis. The etiology of allergic sensitization is poorly understood, and its underlying biological mechanisms are not well established. Several studies showed that DNA methylation (DNAm) at some CpGs is associated with allergic sensitization. However, no studies have focused on the critical adolescence period. Methods We assessed the association of pre- and postadolescence genome-wide DNAm with allergic sensitization against indoor, outdoor and food allergens, using linear mixed models. We hypothesized that DNAm is associated with sensitization in general, and with poly-sensitization status, and these associations are age- and gender-specific. We tested these hypotheses in the IoW cohort (n = 376) and examined the findings in the BAMSE cohort (n = 267). Results Via linear mixed models, we identified 35 CpGs in IoW associated with allergic sensitization (at false discovery rate of 0.05), of which 33 were available in BAMSE and replicated with respect to the direction of associations with allergic sensitization. At the 35 CpGs except for cg19210306 on C13orf27, a reduction in methylation among atopic subjects was observed, most notably for cg21220721 and cg11699125 (ACOT7). DNAm at cg10159529 was strongly correlated with expression of IL5RA in peripheral blood (P-value = 6.76 x 10(-20)). Three CpGs (cg14121142, cg23842695, and cg26496795) were identified in IoW with age-specific association between DNAm and allergic sensitization. Conclusion In adolescence, the status of allergic sensitization was associated with DNAm differentiation and at some CpGs the association is likely to be age-specific.
机译：背景，过敏性敏感性的存在对常见儿童病症如哮喘和鼻炎的发展和过程产生了重大影响。过敏性敏感的病因尚不明白，其潜在的生物机制不是很好的。一些研究表明，一些CPG的DNA甲基化（DNAM）与过敏性敏化有关。然而，没有研究专注于关键青春期。方法我们评估了使用线性混合模型对室内，室外和食品过敏原的过敏性敏化性致敏性敏感性的和过早性致敏化的关联。我们假设Dnam通常与致敏相关，并且具有多敏化状态，这些关联是年龄和性别特异性的。我们在IOW队列（n = 376）中测试了这些假设，并检查了BAMSE队列中的发现（n = 267）。通过线性混合模型的结果，我们在IOW中鉴定了35个与过敏性敏化相关的CPG（以0.05），其中33可在BAMSE中获得，并相对于具有过敏性敏化的关联方向复制。在除C1301030上的CG19210306之外的35个CPG上，观察到应答受试者中甲基化的降低，最值得注意的是CG21220721和CG11699125（ACOT7）。 CG10159529的Dnam与外周血IL5ra的表达强烈相关（P值= 6.76×10（-20））。在IOW中鉴定了三个CPG（CG14121142，CG23842695和CG2649695和CG26496795），其具有特异性的DNAM和过敏性敏化。结论在青春期，过敏性致敏的状态与DNAM分化相关，在一些CPG中，关联可能是特定年龄特异性的。

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