Circulating Level of Monocyte Chemoattractant Protein-1 and Risk of Coronary Artery Disease: A Case–Control and Mendelian Randomization Study

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.