Kang Peiyuan, Wang Zhao, Qiao Dan, Zhang Bohan, Mu Chenyu, Cui Huixian, Li Sha
Clinical Medicine, Hebei Medical University, Shijiazhuang, China.
Department of Anatomy, Hebei Medical University, Shijiazhuang, China.
Front Genet. 2022 Sep 16;13:1019860. doi: 10.3389/fgene.2022.1019860. eCollection 2022.
Alzheimer's disease (AD) and Type 2 Diabetes Mellitus (T2DM) are two of the most common diseases for older adults. Accumulating epidemiological studies suggest that T2DM is a risk factor for cognitive dysfunction in the elderly. In this study, we aimed to dissect the genetic links between the two diseases and identify potential genes contributing the most to the mechanistic link. Two AD (GSE159699 and GSE28146) and two T2DM (GSE38642 and GSE164416) datasets were used to identify the differentially expressed genes (DEGs). The datasets for each disease were detected using two platforms, microarray and RNA-seq. Functional similarity was calculated and evaluated between AD and T2DM DEGs considering semantic similarity, protein-protein interaction, and biological pathways. We observed that the overlapped DEGs between the two diseases are not in a high proportion, but the functional similarity between them is significantly high when considering Gene Ontology (GO) semantic similarity and protein-protein interactions (PPIs), indicating that T2DM shares some common pathways with AD development. Moreover, we constructed a PPI network consisting of AD and T2DM DEGs, and found that the hub gene SLC2A2 (coding transmembrane carrier protein GLUT2), which connects the most DEGs in both AD and T2DM, plays as a key regulator in linking T2DM and AD glucose metabolism related pathways. Through functional evaluation at the systems biology level, we demonstrated that AD and T2DM are similar diseases sharing common pathways and pathogenic genes. SLC2A2 may serve as a potential marker for early warning and monitoring of AD for the T2DM patients.
阿尔茨海默病(AD)和2型糖尿病(T2DM)是老年人中最常见的两种疾病。越来越多的流行病学研究表明,T2DM是老年人认知功能障碍的一个风险因素。在本研究中,我们旨在剖析这两种疾病之间的遗传联系,并确定对机制联系贡献最大的潜在基因。使用了两个AD数据集(GSE159699和GSE28146)和两个T2DM数据集(GSE38642和GSE164416)来识别差异表达基因(DEG)。每种疾病的数据集使用微阵列和RNA测序两个平台进行检测。考虑语义相似性、蛋白质-蛋白质相互作用和生物学途径,计算并评估了AD和T2DM的DEG之间的功能相似性。我们观察到,两种疾病之间重叠的DEG比例不高,但在考虑基因本体(GO)语义相似性和蛋白质-蛋白质相互作用(PPI)时,它们之间的功能相似性显著较高,这表明T2DM与AD的发展共享一些共同途径。此外,我们构建了一个由AD和T2DM的DEG组成的PPI网络,发现连接AD和T2DM中最多DEG的枢纽基因SLC2A2(编码跨膜载体蛋白GLUT2)在连接T2DM和AD的葡萄糖代谢相关途径中起关键调节作用。通过在系统生物学水平上的功能评估,我们证明AD和T2DM是相似的疾病,共享共同途径和致病基因。SLC2A2可能作为T2DM患者AD早期预警和监测的潜在标志物。