摘要： 目的 利用生物信息学方法探索2型糖尿病发病的相关基因，并研究这些基因与阿尔茨海默病的关系。方法 基因表达汇编（GEO）数据库下载GSE85192、GSE95849、GSE97760、GSE85426数据集，获得健康人和2型糖尿病患者外周血的差异基因，利用加权基因共表达网络（WGCNA）分析差异基因和临床性状的关系。使用DAVID数据库分析与2型糖尿病有关的差异基因的功能与相关通路，筛选关键蛋白。根据结果将Toll样受体4（TLR4）作为关键基因，利用基因集富集分析（GSEA）分析GSE97760中与高表达TLR4基因相关的信号通路。通过GSE85426验证TLR4的表达量。结果 富集分析显示，差异基因主要参与的生物学过程包括炎症反应、Toll样受体（TLR）信号通路、趋化因子产生的正向调节等。差异基因主要参与的信号通路有嘧啶代谢通路、TLR信号通路等。ILF2、TLR4、POLR2G、MMP9为2型糖尿病的关键基因。GSEA显示，TLR4上调可通过影响嘧啶代谢及TLR信号通路而导致2型糖尿病及阿尔茨海默病的发生。TLR4在阿尔茨海默病外周血中高表达。结论 ILF2、TLR4、POLR2G、MMP9为2型糖尿病发病的关键基因，TLR4基因上调与2型糖尿病、阿尔茨海默病发生有关。

多芯片联合分析2型糖尿病发病相关基因及其与阿尔茨海默病的关系

辛宁, 陈建康, 陈艳, 杨洁

福建医科大学省立临床医学院, 福建省立医院老年科, 福建省临床老年病研究所, 福州 350001

收稿日期:2020-04-30出版日期:2020-12-30发布日期:2020-12-09
通讯作者:陈建康E-mail:fjslcjk@163.com
作者简介:辛宁(1989-),男,医师,硕士.
基金资助:福建省自然科学基金（2018J01256）


关键词: 2型糖尿病, 阿尔茨海默病, 基因芯片, 胰岛炎症反应, 数据挖掘
Abstract: Objective To use bioinformatics methods to explore genes related to the onset of type 2 diabetes and to study the relationship between these genes and Alzheimer disease. Methods We downloaded the GSE85192,GSE95849,GSE97760,and GSE85426 datasets from the Gene Expression Omnibus (GEO) database. We used R language to obtain differential genes in the peripheral blood of healthy individuals and patients with type 2 diabetes mellitus and used weighted gene co-expression network analysis (WGCNA) to analyze the relationship between these differential genes and clinical traits. The differential genes related to type 2 diabetes were included in the DAVID database to analyze their functions and related pathways and to screen key proteins. According to the results,Toll-like receptor 4(TLR4) was taken as the hub gene,and gene set enrichment analysis (GSEA) was used to analyze the signal pathways related to the high expression of TLR4 in GSE97760. GSE85426 was used to verify the expression of TLR4. Results Enrichment analysis showed that the main biological processes involved in differential genes included inflammatory reaction,toll-like receptor signal pathway,and positive regulation of chemokine production. The main signaling pathways involved in the differential genes were the pyrimidine metabolism pathway,the toll-like receptor signal pathway etc. ILF2,TLR4,POLR2G,and MMP9 were the hub genes of type 2 diabetes. GSEA showed that the upregulation of TLR4 can lead to type 2 diabetes and Alzheimer disease by affecting pyrimidine metabolism and Toll-like receptor signaling pathways. TLR4 is highly expressed in the peripheral blood of Alzheimer disease. Conclusion ILF2,TLR4,POLR2G,and MMP9 were found to be the hub genes of type 2 diabetes. The upregulation of the TLR4 gene was related to the occurrence of type 2 diabetes and Alzheimer disease.
Key words: type 2 diabetes, alzheimer disease, gene chip, islet inflammation, data mining
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