DNA methylation in lung cells is associated with asthma endotypes and genetic risk
DNA methylation in lung cells is associated with asthma endotypes and genetic risk
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DOI：
10.1172/jci.insight.90151
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发表时间：
2016-12-08
期刊：
影响因子：
8
通讯作者：
Ober, Carole
中科院分区：
文献类型：
--
作者：
Nicodemus-Johnson, Jessie;Myers, Rachel A.;Ober, Carole
表观基因组提供了一种底物，通过这种底物，环境暴露可以对基因表达和疾病风险施加影响，但表观遗传变异对人类疾病发生和进展的相对重要性尚不清楚。哮喘是一种气道异质性疾病，其发病和临床过程都是由宿主基因型和环境暴露之间的相互作用引起的，但对这些相互作用的分子机制知之甚少。我们使用Infinium Human methylation 450K Bead Chip评估了全基因组DNA甲基化，并通过RNA测序对74名哮喘和41名非哮喘成人气道上皮细胞的转录组进行了表征。哮喘状况是基于医生的诊断和目前的药物使用情况。使用各种Illumina平台进行基因分型。我们的研究揭示了染色体17q12-21上与哮喘风险和特定哮喘内型和分子网络的表观遗传特征相关的调控位点。总的来说，这些数据支持了肺细胞DNA甲基化的核心作用，它促进了哮喘发病的不同分子途径，并调节了遗传变异对疾病风险和临床异质性的影响。
The epigenome provides a substrate through which environmental exposures can exert their effects on gene expression and disease risk, but the relative importance of epigenetic variation on human disease onset and progression is poorly characterized. Asthma is a heterogeneous disease of the airways, for which both onset and clinical course result from interactions between host genotype and environmental exposures, yet little is known about the molecular mechanisms for these interactions. We assessed genome-wide DNA methylation using the Infinium Human Methylation 450K Bead Chip and characterized the transcriptome by RNA sequencing in primary airway epithelial cells from 74 asthmatic and 41 nonasthmatic adults. Asthma status was based on doctor's diagnosis and current medication use. Genotyping was performed using various Illumina platforms. Our study revealed a regulatory locus on chromosome 17q12-21 associated with asthma risk and epigenetic signatures of specific asthma endotypes and molecular networks. Overall, these data support a central role for DNA methylation in lung cells, which promotes distinct molecular pathways of asthma pathogenesis and modulates the effects of genetic variation on disease risk and clinical heterogeneity.