Wei Mingyu, Hu Xianjing, Zhu Min, Zhang Shuai, Tian Zhenyu, Xie Pengxin, Cui Ming
Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China.
State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
Medicine (Baltimore). 2024 Nov 22;103(47):e40614. doi: 10.1097/MD.0000000000040614.
Studies have shown that uremia, renal failure and heart failure (HF) are closely related. However, whether this association reflects a causal effect is still unclear. The aim of this study was to evaluate the causal effect of uremic metabolites or toxins on HF. Mendelian randomization (MR) analysis was conducted to evaluate the causal effect of 11 uremia-related metabolites on HF risk using single-nucleotide polymorphisms (SNPs) from a genome-wide association study. A protein-protein interaction network was constructed to study the function of SNPs corresponding to HF-related factors. Univariate and multivariate MR analyses demonstrated that lipoprotein A and apolipoprotein B were positively correlated with HF. The SNPs corresponding to these key factors were related mainly to MAP kinase activity and lipid metabolic processes. Overall, we identified 2 uremia-related exposure factors (lipoprotein A and apolipoprotein B) closely related to HF, laying a theoretical foundation for the treatment of HF with renal failure or uremia.
研究表明，尿毒症、肾衰竭和心力衰竭（HF）密切相关。然而，这种关联是否反映因果效应仍不清楚。本研究的目的是评估尿毒症代谢产物或毒素对心力衰竭的因果效应。采用全基因组关联研究中的单核苷酸多态性（SNP），进行孟德尔随机化（MR）分析，以评估11种尿毒症相关代谢产物对心力衰竭风险的因果效应。构建蛋白质-蛋白质相互作用网络，以研究与心力衰竭相关因素对应的SNP的功能。单变量和多变量MR分析表明，脂蛋白A和载脂蛋白B与心力衰竭呈正相关。这些关键因素对应的SNP主要与丝裂原活化蛋白激酶活性和脂质代谢过程有关。总体而言，我们确定了2种与尿毒症相关的暴露因素（脂蛋白A和载脂蛋白B）与心力衰竭密切相关，为治疗肾衰竭或尿毒症合并心力衰竭奠定了理论基础。
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