Qingdao University, Ri Zhao, Shan Dong Province, China.
PLoS One. 2022 Jun 29;17(6):e0270152. doi: 10.1371/journal.pone.0270152. eCollection 2022.
Type 2 diabetes mellitus is a high-risk factor for acute cardiovascular events. Some reports show that Empagliflozin has a protective effect on cardiovascular events and diabetes mellitus, and Empagliflozin can act on the CaMKII pathway. However, the specific gene of action is not precise. Therefore, this study investigated the target genes of Empagliflozin by integrated gene analysis and molecular docking method to provide a theoretical basis for further elucidating the mechanism of action of Empagliflozin.
In this study, we obtained 12 datasets from GEO, divided into experimental and validation groups, with a total of 376 samples. We then integrated CaMKII pathway-related genes from OMIM, NCBI, and genecards databases. We then intersected them with the differential genes we obtained to obtain 5 common genes and performed functional enrichment analysis. We then performed group comparisons in the validation set, and we obtained 2 clinically significant genes. Then we performed group comparison in the validation set, and we obtained 2 clinically significant genes, followed by molecular docking analysis with pymol, autodock software. We obtained molecular docking models for the 2 genes.
In this study, we obtained CaMK2G and PPP1CA, genes associated with the CaMKII pathway and type 2 diabetes and acute cardiovascular events, by integrative gene analysis and validated their expression in the relevant dataset. We also derived that Empagliflozin acts on amino acid TRP-125 of CaMK2G gene and GLN-249 ASP-210 ASP-208 of PPP1CA through CaMKII pathway, thus acting on type 2 diabetes and acute cardiovascular events by molecular docking technique.
2 型糖尿病是急性心血管事件的高危因素。一些报道表明恩格列净对心血管事件和糖尿病具有保护作用，其作用靶点可能与 CaMKII 通路有关，但具体作用的基因并不明确。因此，本研究通过整合基因分析和分子对接的方法，研究恩格列净的作用靶点，为进一步阐明恩格列净的作用机制提供理论依据。
本研究从 GEO 数据库中获取了 12 个数据集，分为实验组和验证组，共 376 例样本。然后从 OMIM、NCBI 和 genecards 数据库中获取 CaMKII 通路相关基因，与我们获得的差异基因取交集，得到 5 个共有基因，进行功能富集分析。在验证组中进行组间比较，得到 2 个有临床意义的基因。然后进行分子对接分析，使用 pymol、autodock 软件，得到这 2 个基因的分子对接模型。
本研究通过整合基因分析和分子对接技术，获得了与 CaMKII 通路和 2 型糖尿病及急性心血管事件相关的 CaMK2G 和 PPP1CA 基因，并在相关数据集验证了其表达。通过分子对接技术，我们还推导出恩格列净通过 CaMKII 通路作用于 CaMK2G 基因的 TRP-125 氨基酸和 PPP1CA 基因的 GLN-249 ASP-210 ASP-208 氨基酸，从而作用于 2 型糖尿病和急性心血管事件。
