Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
The Generation R Study Group, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
Clin Exp Allergy. 2019 Jul;49(7):953-968. doi: 10.1111/cea.13403. Epub 2019 May 14.
Asthma is a common chronic respiratory airway disease influenced by environmental factors and possibly their interaction with the human genome causing epigenetic changes. Epigenome-wide association studies (EWAS) have mainly investigated DNA methylation and its association with disease or traits, exposure factors or gene expression. This systematic review aimed to identify all EWAS assessing differentially methylated sites associated with asthma in humans.
Structured systematic literature search following PRISMA guidelines, Newcastle-Ottawa Scale (NOS) for cohort studies was used for bias assessment.
We searched PubMed and Embase databases from 2005 to 2019.
Epigenome-wide association studies testing association between differential methylation and asthma in humans.
Overall, we identified 16 EWAS studies complying with our search criteria. Twelve studies were conducted on children, and 10 were conducted on sample sizes <150 subjects. Four hundred and nineteen CpGs were reported in children studies after correction for multiple testing. In the adult studies, thousands of differentially methylated sites were identified. Differential methylation in inflammatory-related genes correlated with higher levels of gene expressions of inflammatory modulators in asthma. Differentially methylated genes associated with asthma included SMAD3, SERPINC1, PROK1, IL13, RUNX3 and TIGIT. Forty-one CpGs were replicated at least once in blood samples, and 28 CpGs were replicated in nasal samples.
Although many differentially methylated CpGs in genes known to be involved in asthma have been identified in EWAS to date, we conclude that further studies of larger sample sizes and analyses of differential methylation between different phenotypes are needed in order to comprehensively evaluate the role of epigenetic factors in the pathophysiology and heterogeneity of asthma, and the potential clinical utility to predict or classify patients with asthma.
哮喘是一种常见的慢性呼吸道疾病，受环境因素影响，可能与其导致表观遗传变化的人类基因组相互作用。全基因组关联研究（EWAS）主要研究了 DNA 甲基化及其与疾病或特征、暴露因素或基因表达的关联。本系统评价旨在确定所有评估与人类哮喘相关的差异甲基化位点的 EWAS。
根据 PRISMA 指南进行结构化系统文献检索，使用纽卡斯尔-渥太华量表（NOS）评估队列研究的偏倚。
我们检索了 2005 年至 2019 年的 PubMed 和 Embase 数据库。
检测人类哮喘中差异甲基化与哮喘之间关联的全基因组关联研究。
总体而言，我们确定了 16 项符合我们搜索标准的 EWAS 研究。12 项研究在儿童中进行，10 项研究在样本量<150 例的情况下进行。在经过多次检验校正后，儿童研究报告了 419 个 CpG。在成人研究中，鉴定出数千个差异甲基化位点。与哮喘相关的差异甲基化基因与炎症调节剂的基因表达水平升高相关。与哮喘相关的差异甲基化基因包括 SMAD3、SERPINC1、PROK1、IL13、RUNX3 和 TIGIT。在血液样本中至少有 41 个 CpG 被重复复制，在鼻腔样本中 28 个 CpG 被重复复制。
尽管迄今为止，在 EWAS 中已经鉴定出许多已知与哮喘相关的基因中的差异甲基化 CpG，但我们得出的结论是，需要进一步开展更大样本量的研究，并分析不同表型之间的差异甲基化，以便全面评估表观遗传因素在哮喘的病理生理学和异质性中的作用，以及预测或分类哮喘患者的潜在临床应用。
