代谢物与冠心病：两样本孟德尔随机化研究

Metabolites and coronary heart disease: A two sample Mendelian randomization.

作者信息

Sheng Yang, Gao Feng, Zhu Zhenyu, Zhang Tianjie, Zhang Wei

机构信息

Department of Cardiology, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou, Zhejiang, China.

Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medical College, 88 Jiefang Road, Hangzhou, Zhejiang, China.

出版信息

Int J Cardiol Cardiovasc Risk Prev. 2025 Jan 9;26:200365. doi: 10.1016/j.ijcrp.2025.200365. eCollection 2025 Sep.

BACKGROUND

In observational studies, circulating metabolites were related to Coronary heart disease (CHD), but their causal relationship is unknown. In this study, we sought to determine a bidirectional causal relationship between circulating metabolites and CHD and to explore whether circulating metabolites are associated with a decreased risk of CHD.

METHODS

In our two-sample Mendelian randomization (MR) study, the top SNPs associated with circulating metabolites (n = 24, 925) as well as CHD (n = 86, 995) were acquired from publicly available genome-wide association studies (GWAS). The SNPs estimates were pooled using inverse variance weighted meta-analysis, with median weighted by sensitivity analyses, MR Egger and MR Pleiotropy Residual Sum and Outlier (PRESSO).

RESULTS

Free cholesterol in large LDL(p, 6.9E-07; OR, 2.2; 95%CI,1.6-3.0),total cholesterol in medium LDL(p, 1.0E-06; OR, 1.8; 95%CI,1.4-2.3)Total cholesterol in LDL (p,1.43083E-05; OR,1.7; 95%CI, 1.3-2.2). Phospholipids in medium LDL (p,0.0; OR,1.6; 95%CI, 1.2-2.1); Total cholesterol in small VLDL (p,0.0; OR, 1.8; 95%CI, 1.2-2.7); Triglycerides in small VLDL (p,0.0, OR, 1.3; 95%CI, 1.0-1.6); Free cholesterol in small VLDL (p,0.0; OR,1.3; 95%CI, 1.0-1.7); Phospholipids in small VLDL (p,0.0; OR,1.3, 95%CI,1.0-1.7); Triglycerides in small HDL (p,0.0, OR,1.3,95%CI,1.0-1.7); Alanine (0.0, OR,1.2,95%CI,1.0-1.6) were positively associated with CHD. Phospholipids in medium HDL (p,0.0, OR,0.8; 95%CI, 0.6-0.9) might have a protective effect on CHD, which were negatively associated with CHD.

CONCLUSIONS

Our MR analysis demonstrated a protective effect of Phospholipids in medium HDL, and a potentially anti-protective effect of Free cholesterol in large LDL, Total cholesterol in medium LDL, Total cholesterol in LDL, Phospholipids in medium LDL, Total cholesterol in small VLDL, Triglycerides in small VLDL, Free cholesterol in small VLDL, Phospholipids in small VLDL, Triglycerides in small HDL, Alanine on the pathogenesis of CHD. Additional studies are required to translate the findings into practice.

背景

在观察性研究中，循环代谢物与冠心病（CHD）有关，但其因果关系尚不清楚。在本研究中，我们试图确定循环代谢物与冠心病之间的双向因果关系，并探讨循环代谢物是否与冠心病风险降低相关。

方法

在我们的两样本孟德尔随机化（MR）研究中，从公开可用的全基因组关联研究（GWAS）中获取与循环代谢物（n = 24,925）以及冠心病（n = 86,995）相关的顶级单核苷酸多态性（SNP）。使用逆方差加权荟萃分析汇总SNP估计值，并通过敏感性分析、MR Egger和MR多效性残差和异常值（PRESSO）进行中位数加权。

结果

大低密度脂蛋白中的游离胆固醇（p，6.9E-07；OR，2.2；95%CI，1.6 - 3.0）、中低密度脂蛋白中的总胆固醇（p，1.0E-06；OR，1.8；95%CI，1.4 - 2.3）、低密度脂蛋白中的总胆固醇（p，1.43083E-05；OR，1.7；95%CI，1.3 - 2.2）、中低密度脂蛋白中的磷脂（p，0.0；OR，1.6；95%CI，1.2 - 2.1）、小极低密度脂蛋白中的总胆固醇（p，0.0；OR，1.8；95%CI，1.2 - 2.7）、小极低密度脂蛋白中的甘油三酯（p，0.0，OR，1.3；95%CI，1.0 - 1.6）、小极低密度脂蛋白中的游离胆固醇（p，0.0；OR，1.3；95%CI，1.0 - 1.7）、小极低密度脂蛋白中的磷脂（p，0.0；OR，1.3，95%CI，1.0 - 1.7）、小高密度脂蛋白中的甘油三酯（p，0.0，OR，1.3，95%CI，1.0 - 1.7）、丙氨酸（0.0，OR，1.2，95%CI，1.0 - 1.6）与冠心病呈正相关。中高密度脂蛋白中的磷脂（p，0.0，OR，0.8；95%CI，0.6 - 0.9）可能对冠心病有保护作用，与冠心病呈负相关。

结论

我们的MR分析表明，中高密度脂蛋白中的磷脂具有保护作用，而大低密度脂蛋白中的游离胆固醇、中低密度脂蛋白中的总胆固醇、低密度脂蛋白中的总胆固醇、中低密度脂蛋白中的磷脂、小极低密度脂蛋白中的总胆固醇、小极低密度脂蛋白中的甘油三酯、小极低密度脂蛋白中的游离胆固醇、小极低密度脂蛋白中的磷脂、小高密度脂蛋白中的甘油三酯、丙氨酸对冠心病的发病机制可能具有潜在的反保护作用。需要进一步的研究将这些发现转化为实际应用。