Jia Lili, Zhang Rongqiang
Department of Health Management, School of Humanities and Management, Shaanxi University of Chinese Medicine, Xianyang Shaanxi 712046, China.
Department of Epidemiology and Health Statistics, School of Public Health, Shaanxi University of Chinese Medicine, Xianyang Shaanxi 712046, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 Aug 28;43(8):826-834. doi: 10.11817/j.issn.1672-7347.2018.08.002.
To explore the mechanisms for Type 2 diabetes mellitus (T2DM) in children and provide genomic evidence for its early diagnosis and treatment. Methods: The peripheral blood gene chip datasets from 12 children with T2DM and 24 healthy children were retrieved from the Gene Expression Omnibus (GEO) at National Center for Biotechnology Information (NCBI). The differentially expressed genes were screened by R language software. GenCLiP 2.0, STRING, and Cytoscape software were used to analyze the biological functions, protein-protein interaction network, signal pathway, gene-pathway network, expression of key genes, and predictive value between the two differentially expressed genes. Results: A total of 79 differentially expressed genes were identified. Among them, 58 (73.42%) were up-regulated, and 21 (26.58%) were down-regulated. Differentially expressed genes mainly involved molecular functions and biological processes, such as defensive response, response to external stimulus, and inflammatory responses. At the same time, they were mainly involved in the Leishmaniasis, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway. interleukin 1β (IL-1β), jun proto-oncogene (JUN), and IL-8 were 3 important linking nodes in the protein-protein interaction network. JUN and IL-1β were key genes, which were related to interleukin 17 (1L-17) signaling pathway, Toll-like receptor signaling pathway and so on. The expression of JUN gene in peripheral blood of children with T2DM was decreased while the expression of IL-1β gene was increased. JUN and IL-1β genes possessed certain diagnostic and predictive value in children with T2DM. Conclusion: The gene expression profile of peripheral blood in children with T2DM changes significantly. The genes of JUN and IL-1β are closely related to T2DM in children. IL-1β gene expression level shows a better predictive value on T2DM in children.
探索儿童2型糖尿病（T2DM）的发病机制，为其早期诊断和治疗提供基因组学依据。方法：从美国国立生物技术信息中心（NCBI）的基因表达综合数据库（GEO）中检索12例儿童T2DM患者和24例健康儿童的外周血基因芯片数据集。用R语言软件筛选差异表达基因。利用GenCLiP 2.0、STRING和Cytoscape软件分析差异表达基因的生物学功能、蛋白质-蛋白质相互作用网络、信号通路、基因-通路网络、关键基因表达及两个差异表达基因之间的预测价值。结果：共鉴定出79个差异表达基因。其中，58个（73.42%）上调，21个（26.58%）下调。差异表达基因主要涉及分子功能和生物学过程，如防御反应、对外界刺激的反应和炎症反应。同时，它们主要参与利什曼病、细胞因子-细胞因子受体相互作用、Toll样受体信号通路。白细胞介素1β（IL-1β）、原癌基因jun（JUN）和IL-8是蛋白质-蛋白质相互作用网络中的3个重要连接节点。JUN和IL-1β是关键基因，与白细胞介素17（IL-17）信号通路、Toll样受体信号通路等相关。T2DM患儿外周血中JUN基因表达降低，而IL-1β基因表达升高。JUN和IL-1β基因对T2DM患儿具有一定的诊断和预测价值。结论：T2DM患儿外周血基因表达谱发生显著变化。JUN和IL-1β基因与儿童T2DM密切相关。IL-1β基因表达水平对儿童T2DM具有较好的预测价值。
