Department of Cardiovascular Medicine, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, 210029, Jiangsu Province, China.
Funct Integr Genomics. 2023 Jul 3;23(3):219. doi: 10.1007/s10142-023-01134-9.
This study investigates the interaction between long non-coding RNAs (lncRNAs) and metabolic risk factors that contribute to coronary artery disease (CAD). A total transcriptome high throughput sequencing study was conducted on peripheral blood mononuclear cells from five patients with CAD and five healthy controls. Validation assay by qRT-PCR was conducted among 270 patients and 47 controls. Finally, to evaluate the lncRNAs' diagnostic value for CAD, the Spearman correlation test and receiver operating characteristic curve (ROC) analysis were utilized. Additionally, univariate and multivariate logistic regression along with crossover analyses were conducted to identify the interaction between lncRNA and environmental risk factors. A total of 2149 of 26,027 lncRNAs identified by RNA sequencing were differentially expressed in CAD patients compared to controls. Validation by qRT-PCR showed significantly different relative expression levels for lncRNAs PDXDC1-AS1, SFI1-AS1, RP13-143G15.3, DAPK1-IT1, PPIE-AS1, and RP11-362A1.1 between the two groups (all P<0.05). The area under the ROC values of PDXDC1-AS1 and SFI1-AS1 is 0.645 (sensitivity=0.443 and specificity=0.920) and 0.629 (sensitivity=0.571 and specificity=0.909), especially. Multivariate logistic regression analyses showed that lncRNAs PDXDC1-AS1 (OR=2.285, 95%CI=1.390-3.754, p=0.001) and SFI1-AS1 (OR=1.163, 95%CI=1.163-2.264, p=0.004) were protective factors against CAD. Under the additive model, cross-over analyses demonstrated significant interactions between lncRNAs PDXDC1-AS1 and smoking in relation to CAD risk (S=3.871, 95%CI=1.140-6.599). PDXDC1-AS1 and SFI1-AS1 were sensitive and specific biomarkers for CAD and exhibited synergistic effects with certain environmental factors. These results highlighted their potential use as CAD diagnostic biomarkers for future research.
这项研究旨在探讨长非编码 RNA（lncRNA）与代谢风险因素之间的相互作用，这些因素与冠心病（CAD）的发生有关。我们对 5 例 CAD 患者和 5 例健康对照者的外周血单个核细胞进行了全转录组高通量测序研究。通过 qRT-PCR 在 270 例患者和 47 例对照者中进行了验证试验。最后，为了评估 lncRNA 对 CAD 的诊断价值，我们采用 Spearman 相关检验和受试者工作特征曲线（ROC）分析进行分析。此外，我们还进行了单变量和多变量逻辑回归以及交叉分析，以确定 lncRNA 与环境风险因素之间的相互作用。RNA 测序鉴定的 26027 个 lncRNA 中有 2149 个在 CAD 患者与对照组之间存在差异表达。qRT-PCR 验证显示，lncRNA PDXDC1-AS1、SFI1-AS1、RP13-143G15.3、DAPK1-IT1、PPIE-AS1 和 RP11-362A1.1 在两组之间的相对表达水平差异具有统计学意义（均 P<0.05）。PDXDC1-AS1 和 SFI1-AS1 的 ROC 曲线下面积分别为 0.645（敏感性=0.443，特异性=0.920）和 0.629（敏感性=0.571，特异性=0.909）。多变量逻辑回归分析显示，lncRNA PDXDC1-AS1（OR=2.285，95%CI=1.390-3.754，p=0.001）和 SFI1-AS1（OR=1.163，95%CI=1.163-2.264，p=0.004）是 CAD 的保护性因素。在加性模型下，交叉分析显示，lncRNA PDXDC1-AS1 与吸烟之间存在与 CAD 风险相关的显著相互作用（S=3.871，95%CI=1.140-6.599）。PDXDC1-AS1 和 SFI1-AS1 是 CAD 的敏感和特异性生物标志物，并且与某些环境因素具有协同作用。这些结果强调了它们作为未来 CAD 诊断生物标志物的潜在用途。
