Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin, China.
Front Endocrinol (Lausanne). 2024 Apr 23;15:1383772. doi: 10.3389/fendo.2024.1383772. eCollection 2024.
ASCVD is the primary cause of mortality in individuals with T2DM. A potential link between ASCVD and T2DM has been suggested, prompting further investigation.
We utilized linear and multivariate logistic regression, Wilcoxon test, and Spearman's correlation toanalyzethe interrelation between ASCVD and T2DM in NHANES data from 2001-2018.The Gene Expression Omnibus (GEO) database and Weighted Gene Co-expression Network Analysis (WGCNA) wereconducted to identify co-expression networks between ASCVD and T2DM. Hub genes were identified using LASSO regression analysis and further validated in two additional cohorts. Bioinformatics methods were employed for gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, along with the prediction of candidate small molecules.
Our analysis of the NHANES dataset indicated a significant impact of blood glucose on lipid levels within diabetic cohort, suggesting that abnormal lipid metabolism is a critical factor in ASCVD development. Cross-phenotyping analysis revealed two pivotal genes, ABCC5 and WDR7, associated with both T2DM and ASCVD. Enrichment analyses demonstrated the intertwining of lipid metabolism in both conditions, encompassing adipocytokine signaling pathway, fatty acid degradation and metabolism, and the regulation of adipocyte lipolysis. Immune infiltration analysis underscored the involvement of immune processes in both diseases. Notably, RITA, ON-01910, doxercalciferol, and topiramate emerged as potential therapeutic agents for both T2DM and ASCVD, indicating their possible clinical significance.
Our findings pinpoint ABCC5 and WDR7 as new target genes between T2DM and ASCVD, with RITA, ON-01910, doxercalciferol, and topiramate highlighted as promising therapeutic agents.
ASCVD 是 T2DM 患者死亡的主要原因。ASCVD 和 T2DM 之间可能存在联系，这促使我们进一步进行了研究。
我们利用线性和多变量逻辑回归、Wilcoxon 检验和 Spearman 相关分析，在 2001-2018 年 NHANES 数据中分析 ASCVD 和 T2DM 之间的相互关系。利用基因表达综合数据库（GEO）和加权基因共表达网络分析（WGCNA），确定 ASCVD 和 T2DM 之间的共表达网络。使用 LASSO 回归分析识别 hub 基因，并在另外两个队列中进行验证。利用生物信息学方法进行基因本体论和京都基因与基因组百科全书（KEGG）通路富集分析，并预测候选小分子。
我们对 NHANES 数据集的分析表明，血糖对糖尿病患者群体中脂质水平有显著影响，提示脂质代谢异常是 ASCVD 发展的关键因素。跨表型分析揭示了两个关键基因 ABCC5 和 WDR7，它们与 T2DM 和 ASCVD 都有关联。富集分析表明，两种情况下的脂质代谢相互交织，包括脂肪细胞因子信号通路、脂肪酸降解和代谢以及脂肪细胞脂解的调节。免疫浸润分析强调了两种疾病中免疫过程的参与。值得注意的是，RITA、ON-01910、 doxercalciferol 和托吡酯被认为是 T2DM 和 ASCVD 的潜在治疗药物，表明它们可能具有临床意义。
我们的研究结果确定了 ABCC5 和 WDR7 是 T2DM 和 ASCVD 之间的新靶基因，RITA、ON-01910、 doxercalciferol 和托吡酯是有前途的治疗药物。
