Mohan Sachin, Mok Shaffer, Judge Thomas
Department of Gastroenterology and Hepatology, University of Minnesota School of Medicine, St Paul, MN, USA.
Regions Hospital, Department of Gastroenterology and Hepatology, St Paul, MN, USA.
Clin Exp Gastroenterol. 2020 Oct 19;13:467-473. doi: 10.2147/CEG.S264812. eCollection 2020.
Utilization of genetic databases to identify genes involved in ulcerative colitis (UC), Crohn's disease (CD), and their extra-intestinal manifestations.
Protein coding genes involved in ulcerative colitis (3783 genes), Crohn's disease (3980 genes), uveitis (1043 genes), arthritis (5583 genes), primary sclerosing cholangitis (PSC) (1313 genes), and pyoderma gangrenosum (119 genes) were categorized using four genetic databases. These include Genecards: The Human Gene Database (www.genecards.org), DisGeNET (https://www.disgenet.org/), The Comparative Toxicogenomics Database (http://ctdbase.org/) and the Universal Protein Resource (https://www.uniprot.org/). NDex, Network Data Exchange (http://www.ndexbio.org/), was then utilized for mapping a unique signal pathway from the identified shared genes involved in the above disease processes.
We have detected a unique array of 20 genes with the highest probability of overlay in UC, CD, uveitis, arthritis, pyoderma gangrenosum, and PSC. Figure 1 represents the interactome of these 20 protein coding genes. Of note, unique immune modulators in different disease processes are also noted. Interleukin-25 (IL-25) and monensin-resistant homolog 2 (MON-2) are only noted in UC, CD, pyoderma gangrenosum, and arthritis. Arachidonate 5-lipoxygenase (ALOX5) is involved in UC, CD, and arthritis. SLCO1B3 is exclusively involved with pyoderma gangrenosum, UC, and CD. As expected, TNF involvement is noted in CD, UC, PSC, and arthritis. Table 1 depicts the detailed result.
Our work has identified a distinctive set of genes involved in IBD and its associated extra-intestinal disease processes. These genes play crucial roles in mechanisms of immune response, inflammation, and apoptosis and further our understanding of this complex disease process. We postulate that these genes play a critical role at intersecting pathways involved in inflammatory bowel disease, and these novel molecules, their upstream and downstream effectors, are potential targets for future therapeutic agents.
利用基因数据库鉴定参与溃疡性结肠炎（UC）、克罗恩病（CD）及其肠外表现的基因。
利用四个基因数据库对参与溃疡性结肠炎（3783个基因）、克罗恩病（3980个基因）、葡萄膜炎（1043个基因）、关节炎（5583个基因）、原发性硬化性胆管炎（PSC）（1313个基因）和坏疽性脓皮病（119个基因）的蛋白质编码基因进行分类。这些数据库包括：基因卡片：人类基因数据库（www.genecards.org）、疾病基因网络数据库（https://www.disgenet.org/）、比较毒理基因组学数据库（http://ctdbase.org/）和通用蛋白质资源数据库（https://www.uniprot.org/）。然后利用网络数据交换平台NDex（http://www.ndexbio.org/），从上述疾病过程中鉴定出的共享基因中绘制出独特的信号通路。
我们检测到一组独特的20个基因，它们在UC、CD、葡萄膜炎、关节炎、坏疽性脓皮病和PSC中重叠的可能性最高。图1展示了这20个蛋白质编码基因的相互作用组。值得注意的是，在不同疾病过程中还发现了独特的免疫调节剂。白细胞介素-25（IL-25）和耐莫能菌素同源物2（MON-2）仅在UC、CD、坏疽性脓皮病和关节炎中被发现。花生四烯酸5-脂氧合酶（ALOX5）参与UC、CD和关节炎。溶质载体有机阴离子转运体家族1成员B3（SLCO1B3）仅与坏疽性脓皮病、UC和CD有关。正如预期的那样，肿瘤坏死因子（TNF）参与了CD、UC、PSC和关节炎。表1展示了详细结果。
我们的研究确定了一组与炎症性肠病及其相关肠外疾病过程相关的独特基因。这些基因在免疫反应、炎症和细胞凋亡机制中发挥关键作用，加深了我们对这一复杂疾病过程的理解。我们推测这些基因在炎症性肠病相关的交叉通路中起关键作用，这些新分子及其上下游效应器是未来治疗药物的潜在靶点。
