Zhang Yu, Tan Meiyu, Qian Xiaoqiong, Li Cong, Yue Lei, Liu Yuehong, Shi Song
Department of Otorhinolaryngology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, China.
Department of Laboratory Diagnosis, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, China.
Allergy Asthma Clin Immunol. 2021 May 1;17(1):44. doi: 10.1186/s13223-021-00526-5.
Recent research has pointed out the important roles of epigenetic modifications in the development and persistence of allergic rhinitis (AR), especially in relation to DNA methylation of disease-associated genes. We investigated whether AR susceptibility genes were epigenetically regulated, and whether methylation modulation of these genes in response to early-life environment could be a molecular mechanism underlying the risk for AR onset in a cohort of children aged 3-6 years in China.
Peripheral blood mononuclear cell (PBMC) samples were collected from 130 children patients, aged 3-6 years and diagnosed with AR; and 154 matched controls to detect promoter methylation in 25 AR susceptibility genes with the MethylTarget approach. Methylation levels were compared for each CpG site, each amplified region, and each gene. In addition, the relationship among DNA methylation, early-life environmental risk factors and AR onset were assessed.
Maternal allergic history (P = 0.0390) and pet exposure (P = 0.0339) were significantly associated with increased AR risk. Differential methylation analyses were successfully performed for 507 CpG sites, 34 amplified regions and 17 genes and significant hypomethylation was observed in the promoter region of ADAM33 in AR patients [multiple test-corrected (FDR) P-value < 0.05]. Spearman correlation analysis revealed that the hypomethylation of ADAM33 was significantly associated with higher eosinophil counts (Spearman's ρ: - 0.187, P-value = 0.037). According to the results of the multiple regression analysis, after adjusting for cofounders, the interaction of early-life pet exposure with methylation level of ADAM33 increased the risk for AR onset 1.423 times more in children (95% CI = 0.0290-4.109, P-value = 0.005).
This study provides evidence that early-life pet exposure and low methylation level of ADAM33 increase AR risk in children, and the interaction between pet exposure and methylation level of ADAM33 may play an important role in the development of AR.
近期研究指出表观遗传修饰在变应性鼻炎（AR）的发生和持续存在中发挥重要作用，尤其是与疾病相关基因的DNA甲基化有关。我们调查了AR易感基因是否受到表观遗传调控，以及这些基因在应对早期生活环境时的甲基化调节是否可能是中国3至6岁儿童队列中AR发病风险的潜在分子机制。
收集130例年龄在3至6岁且诊断为AR的儿童患者以及154例匹配对照的外周血单个核细胞（PBMC）样本，采用甲基化靶向方法检测25个AR易感基因的启动子甲基化情况。比较每个CpG位点、每个扩增区域和每个基因的甲基化水平。此外，评估DNA甲基化、早期生活环境危险因素与AR发病之间的关系。
母亲过敏史（P = 0.0390）和宠物接触史（P = 0.0339）与AR风险增加显著相关。成功对507个CpG位点、34个扩增区域和17个基因进行了差异甲基化分析，在AR患者中观察到ADAM33启动子区域显著低甲基化[多重检验校正（FDR）P值<0.05]。Spearman相关性分析显示，ADAM33的低甲基化与较高的嗜酸性粒细胞计数显著相关（Spearman相关系数ρ：-0.187，P值 = 0.037）。根据多元回归分析结果，在调整混杂因素后，早期生活宠物接触与ADAM33甲基化水平的相互作用使儿童AR发病风险增加1.423倍（95%置信区间 = 0.0290 - 4.109，P值 = 0.005）。
本研究提供了证据表明，早期生活宠物接触和ADAM33低甲基化水平会增加儿童AR风险，宠物接触与ADAM33甲基化水平之间的相互作用可能在AR的发生发展中起重要作用。
