Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
National Anti-Drug Laboratory, Shaanxi Regional Center, Xi'an 712000, China.
Nutrients. 2024 Oct 22;16(21):3588. doi: 10.3390/nu16213588.
Acute acalculous cholecystitis (AAC) is a type of cholecystitis with high mortality rate while its pathogenesis remains complex. Choline is one of the essential nutrients and is related to several diseases. This study aimed to explore the causal relationship between choline metabolites and AAC and its potential mechanisms.
This research utilized the two-sample Mendelian randomization method to investigate the causal relationship between choline metabolites and AAC. Additionally, multivariable Mendelian randomization and mediated Mendelian randomization were used to explore potential confounding effects from low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TGs), and coronary artery disease (CAD). Linkage disequilibrium score regression (LDSC), co-localization analysis, and enrichment analysis were used to investigate relevant molecular mechanisms.
There is a negative causal relationship between total choline (OR [95%CI] = 0.9982 [0.9974, 0.9990], = 0.0023), phosphatidylcholine (OR [95%CI] = 0.9983 [0.9976-0.9991], = 0.0040), sphingomyelin (OR [95%CI] = 0.9980 [0.9971-0.9988], = 0.0001), and AAC. The mediating effects of LDL were -0.0006 for total choline, -0.0006 for phosphatidylcholine, and -0.0008 for sphingomyelin, indicating a protective effect of total choline, phosphatidylcholine, and sphingomyelin on AAC. Colocalized SNP rs75331444, which is mapped to gene , was identified for total choline (PPH4 = 0.8778) and sphingomyelin (PPH4 = 0.9344).
There is a causal relationship between choline metabolites and cholecystitis, mediated through the protective action of LDL. Our results suggest that may play a role in the development of non-calculous cholecystitis.
急性非结石性胆囊炎（AAC）是一种死亡率较高的胆囊炎，其发病机制仍较为复杂。胆碱是一种必需营养素，与多种疾病有关。本研究旨在探讨胆碱代谢物与 AAC 之间的因果关系及其潜在机制。
本研究采用两样本孟德尔随机化方法研究胆碱代谢物与 AAC 之间的因果关系。此外，还采用多变量孟德尔随机化和介导孟德尔随机化来探讨来自低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、甘油三酯（TGs）和冠心病（CAD）的潜在混杂效应。连锁不平衡得分回归（LDSC）、共定位分析和富集分析用于研究相关的分子机制。
总胆碱（OR [95%CI] = 0.9982 [0.9974, 0.9990]， = 0.0023）、磷脂酰胆碱（OR [95%CI] = 0.9983 [0.9976-0.9991]， = 0.0040）、鞘磷脂（OR [95%CI] = 0.9980 [0.9971-0.9988]， = 0.0001）与 AAC 呈负相关。总胆碱的 LDL 介导效应为-0.0006，磷脂酰胆碱为-0.0006，鞘磷脂为-0.0008，表明总胆碱、磷脂酰胆碱和鞘磷脂对 AAC 具有保护作用。共定位 SNP rs75331444 映射到基因 ，被鉴定为总胆碱（PPH4 = 0.8778）和鞘磷脂（PPH4 = 0.9344）。
胆碱代谢物与胆囊炎之间存在因果关系，这种关系是通过 LDL 的保护作用介导的。我们的研究结果表明 可能在非结石性胆囊炎的发展中发挥作用。
