Song Yanmin, Cao Liping, Long Hui
Emergency Department, Xiangya Hospital, Central South University, Xiangya Road, Changsha , Hunan, 410008, China.
Thromb J. 2025 Jan 20;23(1):5. doi: 10.1186/s12959-025-00691-2.
α-Klotho may involve in the occurrence and development of venous thromboembolism (VTE). However, the underlying relationship between circulating α-Klotho levels and VTE is still unclear.
This two-sample Mendelian Randomization (MR) study aims to explore the causal associations of circulating α-Klotho levels with different types of venous thromboembolism. Data of exposure and outcomes were extracted from the genome-wide association study (GWAS) of the MRC Integrative Epidemiology Unit (MRC-IEU). The fixed inverse variance weighted (IVW), MR-Egger, MR-Robust Adjusted Profile Score (RAPS) and the weighted-median methods were utilized to investigate the causal associations of circulating α-Klotho levels with different types of VTE. The effect size was expressed as odds ratios (ORs) and 95% confidence intervals (CIs), and the False Discovery Rate (FDR) test was used for correction. The MR scatter plot and leave-one-out test were used for sensitivity analysis. In addition, reverse causal associations were assessed.
IVW estimates suggested that an elevated circulating α-Klotho level was associated with lower odds of deep vein thrombosis (DVT) of lower extremities (OR = 0.992, 95%CI: 0.986-0.998, P = 0.0074), pulmonary embolism (PE) (OR = 0.474, 95%CI: 0.255-0.881, P = 0.0183), and DVT of lower extremities combined with PE (OR = 0.984, 95%CI: 0.971-0.997, P = 0.0175). However, after the FDR correction, only negatively causal association between circulating α-Klotho level and increased odds of lower-extremity DVT was statistically significant (FDR P = 0.0296). Also, there were no reverse causal associations between the circulating α-Klotho levels and different types of VTE (all P > 0.05). Additionally, both the MR scatter plots and leave-one-out test results showed that these causal associations were relatively robust.
An elevated circulating α-Klotho levels was associated with lower risk of DVT of lower extremities, PE, and DVT of lower extremities combined with PE, indicating α-Klotho has the potential to act as a target for early screening or treatment for VTE. However, the specific mechanism that α-Klotho influencing the occurrence of VTE still needed further exploration.
α-klotho可能参与静脉血栓栓塞症（VTE）的发生和发展。然而，循环α-klotho水平与VTE之间的潜在关系仍不清楚。
这项两样本孟德尔随机化（MR）研究旨在探讨循环α-klotho水平与不同类型静脉血栓栓塞症之间的因果关联。暴露和结局数据从MRC综合流行病学单位（MRC-IEU）的全基因组关联研究（GWAS）中提取。采用固定逆方差加权（IVW）、MR-Egger、MR稳健调整轮廓评分（RAPS）和加权中位数方法来研究循环α-klotho水平与不同类型VTE之间的因果关联。效应大小以比值比（OR）和95%置信区间（CI）表示，并使用错误发现率（FDR）检验进行校正。MR散点图和留一法检验用于敏感性分析。此外，还评估了反向因果关联。
IVW估计表明，循环α-klotho水平升高与下肢深静脉血栓形成（DVT）的较低几率相关（OR = 0.992，95%CI：0.986 - 0.998，P = 0.0074）、肺栓塞（PE）（OR = 0.474，95%CI：0.255 - 0.881，P = 0.0183）以及下肢DVT合并PE（OR = 0.984，95%CI：0.971 - 0.997，P = 0.0175）。然而，经过FDR校正后，仅循环α-klotho水平与下肢DVT几率增加之间的负向因果关联具有统计学意义（FDR P = 0.0296）。此外，循环α-klotho水平与不同类型VTE之间不存在反向因果关联（所有P > 0.05）。另外，MR散点图和留一法检验结果均表明这些因果关联相对稳健。
循环α-klotho水平升高与下肢DVT、PE以及下肢DVT合并PE的较低风险相关，表明α-klotho有潜力作为VTE早期筛查或治疗的靶点。然而，α-klotho影响VTE发生的具体机制仍需进一步探索。
