Department of Cardiology, The Second Hospital of Shanxi Medical University, School of Medicine, Shanxi Medical University, Taiyuan, China.
Department of Cardiology, The Frist Hospital of Shanxi Medical University, School of Medicine, Shanxi Medical University, Taiyuan, China.
Medicine (Baltimore). 2024 Oct 11;103(41):e39789. doi: 10.1097/MD.0000000000039789.
Coronary heart disease (CHD) is a global health concern, with inflammation significantly contributing to its pathogenesis. It is crucial to understand the relationship between inflammatory cytokines and CHD. This study investigates the causal correlations between circulating inflammatory cytokines and CHD using Mendelian randomization (MR), assessing both causative and resultant roles of these cytokines in CHD. In this bidirectional MR analysis, we used genetic data from a genome-wide association study (GWAS) of 60,801 CHD cases and 123,504 controls of European ancestry. We derived inflammatory cytokine data from a GWAS summary of 14,824 participants. The primary analytical approach was the inverse variance-weighted (IVW) method, supported by MR-Egger, weighted median, and weighted mode analyses. Heterogeneity was assessed using the Cochrane Q test, and horizontal pleiotropy was evaluated through the MR-Egger intercept and the MR-PRESSO global test, ensuring robustness against potential pleiotropic bias. This study pinpointed several cytokines as key upstream influencers on the risk of CHD, including eotaxin (CCL11) (odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.03-1.18, P = .003), C-C motif chemokine ligand 20 (CCL20) (OR: 1.15, 95% CI: 1.05-1.25, P = .002), macrophage colony-stimulating factor 1 (CSF1) (OR: 1.09, 95% CI: 1.01-1.17, P = .020), Fibroblast growth factor 21 (FGF21) (OR: 1.14, 95% CI: 1.01-1.29, P = .038), Fms-related tyrosine kinase 3 ligand (FLT3LG) (OR: 1.26, 95% CI: 1.09-1.44, P = .001), neurotrophin-3 (NT-3) (OR: 1.12, 95% CI: 1.01-1.24, P = .026), and leukemia inhibitory factor (LIF) (OR: 0.89, 95% CI: 0.80-0.99, P = .029). Conversely, T-cell surface glycoprotein CD5 (CD5) (beta: -0.15, 95% CI: -0.29 to -0.01, P = .042) were identified as downstream factors impacted by CHD. No evidence of heterogeneity or horizontal pleiotropy was detected across all results, and a leave-one-out analysis substantiated the robustness of these findings. These findings suggest that CCL11, CCL20, CSF1, FGF21, FLT3LG, NT-3, and LIF may play a crucial role in the pathogenesis of CHD. Additionally, CHD may impact the expression of CD5. Additional research is needed to explore the potential of these biomarkers in the prevention and treatment of CHD.
冠心病（CHD）是一个全球性的健康问题，炎症在其发病机制中起着重要作用。了解炎症细胞因子与 CHD 之间的关系至关重要。本研究使用孟德尔随机化（MR）方法研究了循环炎症细胞因子与 CHD 之间的因果关系，评估了这些细胞因子在 CHD 中的因果作用和结果作用。在这项双向 MR 分析中，我们使用了欧洲血统的 60801 例 CHD 病例和 123504 例对照的全基因组关联研究（GWAS）的遗传数据。我们从 14824 名参与者的 GWAS 汇总中得出了炎症细胞因子数据。主要分析方法是逆方差加权（IVW）方法，辅之以 MR-Egger、加权中位数和加权模式分析。使用 Cochrane Q 检验评估异质性，使用 MR-Egger 截距和 MR-PRESSO 全局检验评估水平性偏倚，以确保对潜在的偏倚具有稳健性。本研究确定了几种细胞因子作为 CHD 风险的关键上游影响因素，包括嗜酸性粒细胞趋化因子（CCL11）（比值比 [OR]：1.10，95%置信区间 [CI]：1.03-1.18，P =.003）、C-C 基序趋化因子配体 20（CCL20）（OR：1.15，95%CI：1.05-1.25，P =.002）、巨噬细胞集落刺激因子 1（CSF1）（OR：1.09，95%CI：1.01-1.17，P =.020）、成纤维细胞生长因子 21（FGF21）（OR：1.14，95%CI：1.01-1.29，P =.038）、Fms 相关酪氨酸激酶 3 配体（FLT3LG）（OR：1.26，95%CI：1.09-1.44，P =.001）、神经生长因子 3（NT-3）（OR：1.12，95%CI：1.01-1.24，P =.026）和白血病抑制因子（LIF）（OR：0.89，95%CI：0.80-0.99，P =.029）。相反，T 细胞表面糖蛋白 CD5（CD5）（beta：-0.15，95%CI：-0.29 至-0.01，P =.042）被确定为受 CHD 影响的下游因素。所有结果均未检测到异质性或水平性偏倚，单样本分析证实了这些发现的稳健性。这些发现表明，CCL11、CCL20、CSF1、FGF21、FLT3LG、NT-3 和 LIF 可能在 CHD 的发病机制中发挥关键作用。此外，CHD 可能会影响 CD5 的表达。需要进一步研究来探索这些生物标志物在 CHD 预防和治疗中的潜力。
