Chen Yang, Zhu Jiayi, Guo Xin, Cao Chenghui, Xiao Xuan, Zhu Botao, Weng Shuwei, Hu Die, Luo Yonghong, Wang Shuai, Wu Sha, He Jia, Yang Yang, Peng Daoquan
Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.
Research Institute of Blood Lipid and Atherosclerosis, Central South University, Changsha, China.
Front Endocrinol (Lausanne). 2024 Feb 26;15:1361416. doi: 10.3389/fendo.2024.1361416. eCollection 2024.
Recent studies have revealed a significant decrease in serum fetuin-A levels in atherosclerotic aneurysms, indicating that fetuin-A may play a protective role in the progression of arterial calcification. However, the specific mechanism behind this phenomenon remains unclear. We aimed to examine the association between fetuin-A levels in thoracic aortic aneurysms (TAAs) and risk of TAAs and to evaluate whether this association was causal.
A total of 26 SNPs were selected as instrumental variables for fetuin-A in 9,055 participants of European ancestry from the CHARGE consortium, and their effects on thoracic aortic aneurysm and decreased descending thoracic aortic diameter were separately estimated in 353,049 and 39,688 individuals from FinnGen consortium. We used two-sample Mendelian randomization (MR) analysis to examine the causal association. At the same time, we employed various methods, including random-effects inverse variance weighting, weighted median, MR Egger regression, and MR PRESSO, to ensure the robustness of causal effects. We assessed heterogeneity using Cochran's Q value and examined horizontal pleiotropy through MR Egger regression and retention analysis.
Fetuin-A level was associated with a significantly decreasing risk of thoracic aortic aneurysm (odds ratio (OR) 0.64, 95% CI 0.47 - 0.87, = 0.0044). Genetically predicted fetuin-A was also correlated with the decreased descending thoracic aortic diameter (β = -0.086, standard error (SE) 0.036, = 0.017).
Serum fetuin-A level was negatively associated with risk of TTAs and correlated with the decreased descending thoracic aortic diameter. Mendelian randomization provides support for the potential causal relationship between fetuin-A and thoracic aortic aneurysm.
最近的研究表明，动脉粥样硬化性动脉瘤患者血清胎球蛋白-A水平显著降低，这表明胎球蛋白-A可能在动脉钙化进展中起保护作用。然而，这一现象背后的具体机制仍不清楚。我们旨在研究胸主动脉瘤（TAA）患者胎球蛋白-A水平与TAA风险之间的关联，并评估这种关联是否具有因果关系。
从CHARGE联盟中选取9055名欧洲血统参与者的26个单核苷酸多态性（SNP）作为胎球蛋白-A的工具变量，并在FinnGen联盟的353049名和39688名个体中分别评估它们对胸主动脉瘤和降主动脉直径减小的影响。我们采用两样本孟德尔随机化（MR）分析来检验因果关联。同时，我们采用了多种方法，包括随机效应逆方差加权、加权中位数、MR Egger回归和MR PRESSO，以确保因果效应的稳健性。我们使用Cochran's Q值评估异质性，并通过MR Egger回归和保留分析检查水平多效性。
胎球蛋白-A水平与胸主动脉瘤风险显著降低相关（比值比（OR）为0.64，95%置信区间为0.47 - 0.87，P = 0.0044）。基因预测的胎球蛋白-A也与降主动脉直径减小相关（β = -0.086，标准误（SE）为0.036，P = 0.017）。
血清胎球蛋白-A水平与TAA风险呈负相关，并与降主动脉直径减小相关。孟德尔随机化为胎球蛋白-A与胸主动脉瘤之间的潜在因果关系提供了支持。
