RT期刊文章SR电子T1联合甲基化分析肺组织确定胎儿源性COPD途径JF欧洲呼吸杂志JO Eur Respir J FD欧洲呼吸学会SP 1902347 DO 10.1181 /13993003.02347-2019 A1 Kachroo, Priyadarshini A1 Morrow, Jarrett D. A1 Kho, Alvin T188bet官网地址. A1 Vyhlidal, Carrie A. A1 Silverman, Edwin K. A1 Weiss, Scott T. A1 Tantisira, Kelan G. A1 DeMeo，Dawn L. YR 2020 UL //www.qdcxjkg.com/content/early/2020/05/26/13993003.02347-2019.abstract AB慢性阻塞性肺疾病(COPD)可能有发育起源，但潜在的分子机制尚未完全确定。使用网络方法对肺组织特异性表观遗传修饰(如DNA甲基化)的研究可能有助于洞察子宫内烟雾(IUS)暴露与成年期COPD风险之间的联系。我们对160例手术样本和78例从妊娠8至18周的废弃组织中分离的胎儿肺DNA样本进行了全基因组甲基化分析。构建共甲基化网络，以识别在胎儿和成人肺组织中共享甲基化模式的保留模块，并与胎儿IUS暴露、孕龄和COPD相关。加权相关网络突出了胎儿和成人肺数据的保存和共甲基化模块，这些数据与胎儿ius暴露、COPD和成人肺功能较低有关。这些模块中涉及胚胎器官发育和特定炎症相关通路的基因显著富集，包括Hippo、PI3K/AKT、Wnt、MAP-Kinase和tgf - β信号通路。与妊娠年龄相关的模块显著保留了COPD和肺功能，也注释了Wnt和PI3K/AKT通路富集的基因。暴露于IUS的胎儿肺组织和早期肺发育的表观遗传网络扰动在患有COPD的前吸烟者的成人肺组织中重现。重叠的胎儿和成人肺组织网络模块突出了支持COPD暴露相关和年龄相关发育起源的假定疾病途径。脚注:该手稿最近被《欧洲呼吸杂志》接受发表。在我们的制作团队进行编辑和排版之前，它以被接受的形式发表在这里。在完成这些生产过程并且作者批准了产生的证明之后，本文将转到最新一期的ERJ在线版。 Please open or download the PDF to view this article.Conflict of interest: Dr. Kachroo has nothing to disclose.Conflict of interest: Dr. Morrow reports grants from National Institutes of Health, during the conduct of the study.Conflict of interest: Dr. Kho has nothing to disclose.Conflict of interest: Dr. Vyhlidal reports grants from NIH, during the conduct of the study.Conflict of interest: Dr. Silverman reports grants from NIH, during the conduct of the study; grants and other support from GlaxoSmithKline and grants from Bayer, outside the submitted work.Conflict of interest: Dr. Weiss reports personal fees from UpToDate, outside the submitted work.Conflict of interest: Dr. Tantisira reports grants from National Institutes of Health, during the conduct of the study.Conflict of interest: Dr. DeMeo reports grants from National Institutes of Health, during the conduct of the study and grants from Bayer, outside the submitted work.