Baschal Erin E, Larson Eric D, Bootpetch Roberts Tori C, Pathak Shivani, Frank Gretchen, Handley Elyse, Dinwiddie Jordyn, Moloney Molly, Yoon Patricia J, Gubbels Samuel P, Scholes Melissa A, Cass Stephen P, Jenkins Herman A, Frank Daniel N, Yang Ivana V, Schwartz David A, Ramakrishnan Vijay R, Santos-Cortez Regie Lyn P
Department of Otolaryngology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Department of Pediatric Otolaryngology, Children's Hospital Colorado, Aurora, CO, United States.
Front Genet. 2020 Jan 17;10:1352. doi: 10.3389/fgene.2019.01352. eCollection 2019.
Previous genetic studies on susceptibility to otitis media and airway infections have focused on immune pathways acting within the local mucosal epithelium, and outside of allergic rhinitis and asthma, limited studies exist on the overlaps at the gene, pathway or network level between the upper and lower airways. In this report, we compared [1] pathways identified from network analysis using genes derived from published genome-wide family-based and association studies for otitis media, sinusitis, and lung phenotypes, to [2] pathways identified using differentially expressed genes from RNA-sequence data from lower airway, sinus, and middle ear tissues, in particular cholesteatoma tissue compared to middle ear mucosa. For otitis media, a large number of genes ( = 1,806) were identified as differentially expressed between cholesteatoma and middle ear mucosa, which in turn led to the identification of 68 pathways that are enriched in cholesteatoma. Two differentially expressed genes and overlap in middle ear, sinus, and lower airway samples and are potentially novel genes for otitis media susceptibility. In addition, 56 genes were differentially expressed in both tissues from the middle ear and either sinus or lower airways. Pathways that are common in upper and lower airway diseases, whether from published DNA studies or from our RNA-sequencing analyses, include chromatin organization/remodeling, endocytosis, immune system process, protein folding, and viral process. Taken together, our findings from genetic susceptibility and differential tissue expression studies support the hypothesis that the unified airway theory wherein the upper and lower respiratory tracts act as an integrated unit also applies to infectious and nonallergic airway epithelial disease. Our results may be used as reference for identification of genes or pathways that are relevant to upper and lower airways, whether common across sites, or unique to each disease.
先前关于中耳炎和气道感染易感性的遗传学研究主要集中在局部黏膜上皮内起作用的免疫途径，并且在过敏性鼻炎和哮喘之外，关于上、下气道在基因、途径或网络水平上的重叠的研究有限。在本报告中，我们将[1]使用来自已发表的全基因组家族研究和中耳炎、鼻窦炎及肺部表型关联研究的基因，通过网络分析确定的途径，与[2]使用来自下气道、鼻窦和中耳组织（特别是胆脂瘤组织与中耳黏膜相比）的RNA序列数据中的差异表达基因确定的途径进行了比较。对于中耳炎，大量基因（ = 1806）被确定为在胆脂瘤和中耳黏膜之间差异表达，这进而导致鉴定出68条在胆脂瘤中富集的途径。两个差异表达基因 在中耳、鼻窦和下气道样本中重叠，并且可能是中耳炎易感性的新基因。此外，56个基因在中耳组织以及鼻窦或下气道组织中均差异表达。无论是来自已发表的DNA研究还是我们的RNA测序分析，在上、下气道疾病中共同的途径包括染色质组织/重塑、内吞作用、免疫系统过程、蛋白质折叠和病毒过程。综上所述，我们从遗传易感性和差异组织表达研究中得出的结果支持这样的假设，即上、下呼吸道作为一个整合单元发挥作用的统一气道理论也适用于感染性和非过敏性气道上皮疾病。我们的结果可作为鉴定与上、下气道相关的基因或途径的参考，无论这些基因或途径是跨部位共有的还是每种疾病特有的。
