抽象的
BackgroundThe molecular basis of airway remodeling in chronic obstructive pulmonary disease remains poorly understood. We identified gene expression signatures associated with chest CT scan airway measures to understand molecular pathways associated with airway disease.
方法在COPDGENE研究中的2396名受试者中,我们检查了定量CT气道表型和血液转录组之间的关系,以鉴定气道特异性基因并定义气道壁厚(AWT)基因集评分。进行了多变量回归分析,以确定AWT评分与临床表型,支气管基因表达和遗传变异的关联。
结果Type 1 interferon induced genes were consistently associated with airway wall thickness, Pi10, and wall area percent, with the strongest enrichment in airway wall thickness. A score derived from 18 genes whose expression was associated with AWT was associated with COPD-related phenotypes including reduced lung function (FEV1% predicted −3.4, p<0.05) and increased exacerbations (incidence rate ratio 1.6, p<0.05). The AWT score was reproducibly associated with airway wall thickness in bronchial samples from 23 subjects (beta 3.22, p<0.05). The blood AWT score was associated with genetic variant rs876039, an expression quantitative trait locus (eQTL) forikzf1, a gene which regulates interferon signaling and is associated with inflammatory diseases.
结论带有干扰素的基因表达信号刺激了外周血和支气管刷子的基因与CT气道壁厚,肺功能和恶化有关。共有的基因和遗传关联表明病毒反应和/或自身免疫性失调是COPD气道疾病的潜在基本机制。
脚注
该手稿最近被接受在欧洲呼吸杂志。It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of theERJ在线的。请打开或下载PDF以查看本文。
利益冲突:Yun博士在进行研究期间报告了美国国立卫生研究院的赠款;在提交的工作之外的拜耳赠款;。
利益冲突:李博士没有什么可披露的。
利益冲突:Srinivasa博士没有什么可披露的。
利益冲突:Morrow博士在进行研究期间报告了国立卫生研究院的赠款;。
Conflict of interest: Mr. Chase has nothing to disclose.
利益冲突:Saferali博士没有什么可披露的。
Conflict of interest: Dr. Xu has nothing to disclose.
Conflict of interest: Dr. Cho reports personal fees from Genentech, personal fees from AstraZeneca, personal fees from Illumina, grants from Bayer, grants from GSK, outside the submitted work; .
利益冲突:Castaldi博士报告了GSK的个人费用,GSK的赠款,来自诺华的个人费用,在提交的工作之外;。
利益冲突:赫斯博士报告授予摇来摇去m NHLBI, during the conduct of the study; grants from Boehringer-Ingelheim, grants from Novartis, personal fees from 23andMe, outside the submitted work; .
- 已收到February 23, 2021.
- Accepted2021年9月24日。
- 版权所有©作者2021。用于复制权和权限联系权限{at} ersnet.org