2型糖尿病患儿基因表达谱的改变及其发病机制

Alterations in gene expression profiles in children with Type 2 diabetes mellitus and its mechanisms

目的:探讨儿童2型糖尿病(Type 2 diabetes mellitus,T2DM)的发病机制,为其早期诊断和医治提供基因组学证据。方法:从美国国立生物技术信息中心(National Center for Biotechnology Information,NCBI)的高通量基因表达数据库(gene expression omnibus,GEO)中检索得到12例T2DM患儿和24例健康儿童的外周血基因芯片数据集,利用R语言软件筛选出差异表达基因,并采用Gen CLi P 2.0,STRING及Cytoscape等软件分析两组差异表达基因有关的生物学功能、蛋白质相互作用网络、信号通路、基因-通路相互作用、关键基因的表达状况和预测价值评价。结果:共筛选出79个差异表达基因,其中表达上调的有58个(73.42%),表达下调的有21个(26.58%),差异表达基因主要涉及防御反应、对外刺激反应、炎症应答等分子功能和生物学过程,主要参与利什曼病、细胞因子及其受体的相互作用、Toll样受体信号通路等;白细胞介素1β(interleukin 1 beta,IL-1β)、jun原癌基因(jun proto-oncogene,JUN)和IL-8是蛋白-蛋白相互作用网络中典型子网络的3个重要链接节点;JUN和IL-1β基因是关键基因,其均与1L-17信号通路、Toll样受体信号通路等有关;T2DM患儿外周血的JUN基因表达下降,IL-1β基因表达升高;JUN和IL-1β基因对儿童T2DM均具有一定的诊断和预测价值。结论:T2DM患儿外周血的基因表达谱发生了明显改变,JUN和IL-1β基因与儿童T2DM关系密切,IL-1β基因表达水平对儿童T2DM的预测效果较好。

Objective： 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 pathwa）5 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- 1 ~ were key genes, which were related to interleukin 17 （1L-17） signaling pathway, Toll-like receptor signaling pathway and so on. The expression ofJUN gene in peripheral blood of children with T2DM was decreased while the expression of IL-1βgene was increased. JUN and IL-1βgenes 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.