解放军医学杂志2026，Vol.51Issue(2)：155-163,9.DOI:10.11855/j.issn.0577-7402.0579.1548.2025.1113
循环炎性细胞因子与冠状动脉粥样硬化的因果关系:双向孟德尔随机化研究
Causal relationship between circulating inflammatory cytokines and coronary atherosclerosis:a bidirectional Mendelian randomization study
摘要
Abstract
Objective To explore the causal relationship between circulating inflammatory cytokines and coronary atherosclerosis through bidirectional Mendelian randomization(MR)analysis.Methods The inflammatory cytokine data were sourced from the European population genome-wide protein quantitative trait locus(pQTL)study in the GWAS Catalog database(n=14 824),and the coronary atherosclerosis data were obtained from the FinnGen consortium(n=434 704).Methods including inverse variance weighted(IVW),colocalization analysis,and reverse MR analysis were employed,complemented by MR-Egger and weighted median methods,to comprehensively assess the bidirectional causal relationship between inflammatory cytokines and coronary atherosclerosis.Results Higher levels of interleukin-17C(IL-17C)(OR=1.062,95%CI 1.002-1.126,P=0.044),interleukin-22 receptor subunit A1(IL-22RA1)(OR=1.115,95%CI 1.004-1.239,P=0.042),and matrix metalloproteinase-1(MMP-1)(OR=1.071,95%CI 1.000-1.147,P=0.049)were associated with an increased risk of coronary atherosclerosis.Conversely,higher levels of soluble CD40L(sCD40L)(OR=0.967,95%CI 0.937-0.998,P=0.036),interleukin-24(IL-24)(OR=0.912,95%CI 0.832-0.999,P=0.048),and urokinase-type plasminogen activator(uPA)(OR=0.934,95%CI 0.874-0.999,P=0.045)were associated with a reduced risk of coronary atherosclerosis.Furthermore,the occurrence of coronary atherosclerosis was associated with lower levels of vascular endothelial growth factor-A(VEGF-A)(OR=0.946,95%CI 0.899-0.996,P=0.036),macrophage colony-stimulating factor-1(CSF-1)(OR=0.948,95%CI 0.902-0.996,P=0.033),T-cell surface glycoprotein CD5(OR=0.918,95%CI 0.872-0.966,P=0.001),and eosinophil chemotactic factor(CCL11)(OR=0.952,95%CI 0.908-0.988,P=0.040).Conclusions Elevated levels of IL-17C,IL-22RA1,and MMP-1 are associated with an increased risk of coronary atherosclerosis,whereas elevated levels of sCD40L,IL-24,and uPA are associated with a reduced risk.Moreover,coronary atherosclerosis itself can lower the levels of VEGF-A,CSF-1,CD5,and CCL11.关键词
炎症/细胞因子/冠状动脉粥样硬化/孟德尔随机化Key words
inflammation/circulating inflammatory cytokines/coronary atherosclerosis/Mendelian randomization分类
医药卫生引用本文复制引用
闫浩杰,史树锦,韩帆,宿俊杰,徐帅,衣慧,岳帅,张然..循环炎性细胞因子与冠状动脉粥样硬化的因果关系:双向孟德尔随机化研究[J].解放军医学杂志,2026,51(2):155-163,9.基金项目
This work was supported by the National Key Research and Development Program of China(2021YFC2701700,2021YFC2701703),and the National Natural Science Foundation of China(82171857) 国家重点研发计划(2021YFC2701700,2021YFC2701703) （2021YFC2701700,2021YFC2701703）
国家自然科学基金(82171857) （82171857）
