Guo Qian, Xu Xinghua, Li Xiaohui, Mao Yang, Li Shengqiang, Yao Yuxin, Li Xiang, Li Yaxing, Feng Jiayue, Shu Yan, Xu Xingli
Department of Rhinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
School of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
Front Pharmacol. 2025 Jan 3;15:1514293. doi: 10.3389/fphar.2024.1514293. eCollection 2024.
Abdominal aortic aneurysm (AAA) is one of the most dangerous types of vascular diseases worldwide. Metabolic disturbance affects disease risk and provide underlying therapeutic targets. Previous studies have reported an association between metabolic disorders and AAA. However, evidence of a causal relationship between blood metabolites and AAA is still lacking at present.
Using Mendelian randomization (MR), we assessed the causal association between 1,400 serum metabolites and AAA. The inverse variance weighted method (IVW), weighted median, MR-Egger regression, simple mode, as well as weighted mode methods were used for evaluating the causality between blood metabolites and AAA. Pleiotropy and heterogeneity tests were further conducted.
Through strict screening, 17 known metabolites, 7 unknown metabolites and 5 metabolite ratios related to AAA were identified. Among all the metabolites, 24 were found to have negative associations, while 5 exhibited positive associations. The top five metabolites associated with an increased risk of AAA were Oleoyl-linoleoyl-glycerol (18:1/18:2) [2], Glycosyl-N-(2-hydroxynervonoyl)-sphingosine (d18:1/24:1(2OH)), Glycochenodeoxycholate 3-sulfate, X-21441 and X-24328. In contrast, the top five metabolites that were linked to a reduced risk of AAA included Uridine to pseudouridine ratio, Octadecanedioate, Phosphate to oleoyl-linoleoyl-glycerol (18:1 to 18:2) [2] ratio, 1-(1-enyl-palmitoyl)-GPE (p-16:0), and 1-stearoyl-GPG (18:0).
Among the 1,400 blood metabolites, we identified 17 known metabolites, 7 unknown metabolites, and 5 metabolite ratios associated with AAA. This MR study may provide a novel significant insight for the screening and prevention of AAA.
腹主动脉瘤（AAA）是全球最危险的血管疾病类型之一。代谢紊乱影响疾病风险并提供潜在的治疗靶点。先前的研究报道了代谢紊乱与AAA之间的关联。然而，目前仍缺乏血液代谢物与AAA之间因果关系的证据。
我们使用孟德尔随机化（MR）评估了1400种血清代谢物与AAA之间的因果关联。采用逆方差加权法（IVW）、加权中位数、MR-Egger回归、简单模式以及加权模式方法来评估血液代谢物与AAA之间的因果关系。进一步进行了多效性和异质性检验。
通过严格筛选，鉴定出17种已知代谢物、7种未知代谢物以及5种与AAA相关的代谢物比率。在所有代谢物中，发现24种具有负相关，而5种表现出正相关。与AAA风险增加相关的前五种代谢物是油酰-亚油酰甘油（18:1/18:2）[2]、糖基-N-(2-羟基神经酰胺)-鞘氨醇（d18:1/24:1(2OH)）、甘氨鹅去氧胆酸3-硫酸盐、X-21441和X-24328。相比之下，可以降低AAA风险的前五种代谢物包括尿苷与假尿苷的比率、十八烷二酸、磷酸盐与油酰-亚油酰甘油（18:1至18:2）[2]的比率、1-(1-烯基-棕榈酰)-甘油磷酸乙醇胺（p-16:0）和1-硬脂酰甘油磷酸甘油（18:0）。
在1400种血液代谢物中，我们鉴定出17种已知代谢物、7种未知代谢物以及5种与AAA相关的代谢物比率。这项MR研究可能为AAA的筛查和预防提供新的重要见解。
