Liu Jie, Liu XingDe, Rao Rui, Li Wen
Department of Basic Medical College, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
Department of Cardiology, Longli Hospital of Traditional Chinese Medicine, Qiannan, Guizhou, China.
Medicine (Baltimore). 2025 Feb 14;104(7):e41431. doi: 10.1097/MD.0000000000041431.
This study examines the causal relationship between type 2 diabetes (T2D) and peripheral artery disease (PAD) and their potential mechanisms based on the analysis of the Gene Expression Omnibus database and 2-sample Mendelian randomization (MR). The first part involved a 2-sample MR study and a comprehensive meta-analysis. Differences in the results were assessed using inverse-variance weighting. Heterogeneity was examined using the Cochrane Q statistical test. The leave-one-out method was applied for sensitivity analysis. The potential horizontal pleiotropic effect was assessed using the MR-Egger intercept technique. The second part involved differential gene analysis and weighted gene coexpression network analysis. Subsequently, we overlapped and consolidated the results from the 2 parts to identify the key genes between them. MR analysis results suggested a statistically significant correlation between the incidence of PAD and T2D (odds ratio: 1.22, 95% confidence interval: 1.13-1.32, P = 3.74e-07). We anticipated a pivotal role for TCF7L2 in PAD and T2D. T2D was significantly associated with PAD risk. Simultaneously, the study deepened our understanding of the underlying mechanisms of both diseases, proposing TCF7L2 as a promising target.
本研究基于对基因表达综合数据库和两样本孟德尔随机化（MR）的分析，探讨2型糖尿病（T2D）与外周动脉疾病（PAD）之间的因果关系及其潜在机制。第一部分包括两样本MR研究和全面的荟萃分析。使用逆方差加权评估结果差异。采用Cochrane Q统计检验检查异质性。采用留一法进行敏感性分析。使用MR-Egger截距技术评估潜在的水平多效性效应。第二部分包括差异基因分析和加权基因共表达网络分析。随后，我们将两部分的结果进行重叠和整合，以确定它们之间的关键基因。MR分析结果表明，PAD发病率与T2D之间存在统计学显著相关性（优势比：1.22，95%置信区间：1.13-1.32，P = 3.74e-07）。我们预计TCF7L2在PAD和T2D中起关键作用。T2D与PAD风险显著相关。同时，该研究加深了我们对这两种疾病潜在机制的理解，提出TCF7L2作为一个有前景的靶点。
