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哮喘气道上皮基因表达的荟萃分析。

Meta-analysis of airway epithelium gene expression in asthma.

机构信息

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.

Dept of Genetics, University of North Carolina, Chapel Hill, NC, USA.

出版信息

Eur Respir J. 2018 May 17;51(5). doi: 10.1183/13993003.01962-2017. Print 2018 May.

DOI:10.1183/13993003.01962-2017
PMID:29650561
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7395676/
Abstract

Differential gene expression in the airway epithelium of patients with asthma controls has been reported in several studies. However, there is no consensus on which genes are reproducibly affected in asthma. We sought to identify a consensus list of differentially expressed genes (DEGs) using a meta-analysis approach.We identified eight studies with data that met defined inclusion criteria. These studies comprised 355 cases and 193 controls and involved sampling either bronchial or nasal epithelium. We conducted study-level analyses, followed by a meta-analysis. Likewise, we applied a meta-analysis framework to the results of study-level pathway enrichment.We identified 1273 DEGs, 431 of which had not been identified in previous studies. 450 DEGs exhibited large effect sizes and were robust to study population differences in age, sex, race/ethnicity, medication use, smoking status and exacerbations. The magnitude of differential expression of these 450 genes was highly similar in bronchial and nasal airway epithelia. Meta-analysis of pathway enrichment revealed a number of consistently dysregulated biological pathways, including putative transcriptional and post-transcriptional regulators.In total, we identified a set of genes that is consistently dysregulated in asthma, that links to known and novel biological pathways, and that will inform asthma subtype identification.

摘要

在几项研究中已经报道了哮喘患者和对照者气道上皮细胞中的差异基因表达。然而,在哪些基因在哮喘中可重复地受到影响方面尚无共识。我们试图使用荟萃分析方法来确定一个一致的差异表达基因(DEG)列表。

我们确定了八项符合既定纳入标准的数据研究。这些研究包括 355 例病例和 193 例对照者,涉及支气管或鼻腔上皮细胞的采样。我们进行了研究水平的分析,然后进行了荟萃分析。同样,我们将荟萃分析框架应用于研究水平途径富集的结果。

我们鉴定了 1273 个 DEG,其中 431 个在以前的研究中没有被鉴定。450 个 DEG 表现出大的效应大小,并且对年龄、性别、种族/民族、用药、吸烟状况和加重的研究人群差异具有稳健性。这些 450 个基因的差异表达幅度在支气管和鼻腔气道上皮中非常相似。途径富集的荟萃分析揭示了一些失调的生物学途径,包括假设的转录和转录后调节剂。

总的来说,我们确定了一组在哮喘中一致失调的基因,这些基因与已知和新的生物学途径相关,并将为哮喘亚型的鉴定提供信息。

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本文引用的文献

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Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology.哮喘、花粉热和湿疹的共同遗传起源阐明了过敏性疾病生物学。
Nat Genet. 2017 Dec;49(12):1752-1757. doi: 10.1038/ng.3985. Epub 2017 Oct 30.
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The Nasal Methylome: A Key to Understanding Allergic Asthma.鼻腔甲基化组:理解过敏性哮喘的关键
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An inhaled dose of budesonide induces genes involved in transcription and signaling in the human airways: enhancement of anti- and proinflammatory effector genes.吸入剂量的布地奈德可诱导人类气道中参与转录和信号传导的基因:增强抗炎和促炎效应基因。
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Endogenous Protease Inhibitors in Airway Epithelial Cells Contribute to Eosinophilic Chronic Rhinosinusitis.气道上皮细胞中的内源性蛋白酶抑制剂与嗜酸性慢性鼻-鼻窦炎有关。
Am J Respir Crit Care Med. 2017 Mar 15;195(6):737-747. doi: 10.1164/rccm.201603-0529OC.
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The nasal methylome and childhood atopic asthma.鼻腔甲基化组与儿童特应性哮喘
J Allergy Clin Immunol. 2017 May;139(5):1478-1488. doi: 10.1016/j.jaci.2016.07.036. Epub 2016 Oct 13.
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Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans.人类基因组学。基因型-组织表达(GTEx)试点分析:人类多组织基因调控
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