Li Jing, Zhang Yanqun, Guo Xue, Wu Yuanyuan, Huang Ruo, Han Xia
Department of Health Care, Jinan People's Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, 271100, People's Republic of China.
Department of Cardiology, Jinan People's Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, 271100, People's Republic of China.
Pharmgenomics Pers Med. 2021 May 11;14:553-559. doi: 10.2147/PGPM.S303362. eCollection 2021.
Coronary artery disease (CAD) ranks the leading cause of death worldwide, and inflammation has been implicated in all stages of CAD and is considered to contribute to the pathophysiological basis of atherogenesis.
Here, we implemented a case-control study and a two-sample Mendelian randomization (MR) study to explore the associations between CAD risk and genetic predisposition to circulating level of monocyte chemoattractant protein-1 (MCP1), the most important regulator of monocyte trafficking.
In case-control study, we found circulating level of MCP1 was significantly associated with increased risk of CAD (OR for per quartile increment: 1.33, 95% CI: 1.19-1.49, P<0.001). Further, genetically predicted higher level of MCP1 was significantly associated with higher risk of CAD (OR for 1-SD increase: 1.05, 95% CIs: 1.02-1.08, P value: 0.002) in MR analysis. Sensitivity analyses were also conducted to validate the main findings, and we also did not detect any directional pleiotropy effects using the MR Egger intercept test (P=0.831).
To sum up, our study suggested that increased CAD risk was associated with a predisposition to higher level of MCP1. Additional insight into the contribution of MCP1 to the occurrence of CAD is still needed.
冠状动脉疾病(CAD)是全球首要死因,炎症在CAD各阶段均有涉及,被认为是动脉粥样硬化发病机制的病理生理基础。
在此,我们开展了一项病例对照研究和一项两样本孟德尔随机化(MR)研究,以探究CAD风险与循环单核细胞趋化蛋白-1(MCP1,单核细胞迁移最重要的调节因子)水平的遗传易感性之间的关联。
在病例对照研究中,我们发现MCP1的循环水平与CAD风险增加显著相关(每四分位数增加的OR值:1.33,95%置信区间:1.19 - 1.49,P<0.001)。此外,在MR分析中,遗传预测的较高MCP1水平与较高的CAD风险显著相关(每增加1个标准差的OR值:1.05,95%置信区间:1.02 - 1.08,P值:0.002)。还进行了敏感性分析以验证主要发现,并且我们使用MR Egger截距检验也未检测到任何方向性多效性效应(P = 0.831)。
总之,我们的研究表明CAD风险增加与较高水平的MCP1易感性相关。仍需要对MCP1对CAD发生的贡献有更多深入了解。