Gong Xiaowei, Yuan Yadong
Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, No. 215, Heping West Road, Shijiazhuang, 050000, Hebei Province, China.
Sci Rep. 2025 Jan 2;15(1):7. doi: 10.1038/s41598-024-83735-3.
This study evaluated the causal relationship between matrix metalloproteinases (MMPs) and pulmonary embolism using data from the genome-wide association study (GWAS) of pulmonary embolism from the UK Biobank and a GWAS dataset of MMPs based on 5,457 Icelanders aged 65 years and older. MR-Egger, MR-PRESSO, Cochran's Q, and leave-one-out were used for sensitivity analysis. The Mendelian randomization (MR) analysis, based on the IVW analysis, indicated an elevated risk for pulmonary embolism in association with MMP19 (OR = 1.0009, 95%CI: 1-1.0017, P = 0.041), consistent with the weighted median method results (P = 0.015). In addition, despite the negative result from the IVW method (P = 0.554), the weighted median analysis suggested a reduced risk for pulmonary embolism related to MMP12 (OR = 0.9992, 95%CI: 0.9984-1, P = 0.038). No causal associations were found for the other MMPs (including MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP13, MMP14, MMP16, MMP17, and MMP20) on pulmonary embolism (all P > 0.05). The reverse MR analysis revealed no causal associations between pulmonary embolism as exposure and MMPs as outcomes. Sensitivity analyses confirmed the robustness of these findings. In conclusion, this MR analysis revealed the potential causal relationship between MMPs and pulmonary embolism, suggesting that measuring MMPs could help identify people at higher risk of pulmonary embolism, but further research is needed.
本研究利用来自英国生物银行的肺栓塞全基因组关联研究（GWAS）数据以及基于5457名65岁及以上冰岛人的MMPs的GWAS数据集，评估了基质金属蛋白酶（MMPs）与肺栓塞之间的因果关系。采用MR-Egger、MR-PRESSO、Cochran's Q和留一法进行敏感性分析。基于逆方差加权（IVW）分析的孟德尔随机化（MR）分析表明，与MMP19相关的肺栓塞风险升高（OR = 1.0009，95%CI：1 - 1.0017，P = 0.041），这与加权中位数法的结果一致（P = 0.015）。此外，尽管IVW法得出阴性结果（P = 0.554），但加权中位数分析表明，与MMP12相关的肺栓塞风险降低（OR = 0.9992，95%CI：0.9984 - 1，P = 0.038）。未发现其他MMPs（包括MMP1、MMP2、MMP3、MMP7、MMP8、MMP9、MMP10、MMP13、MMP14、MMP16、MMP-17和MMP20）与肺栓塞之间存在因果关联（所有P > 0.05）。反向MR分析未发现以肺栓塞为暴露因素、MMPs为结局的因果关联。敏感性分析证实了这些发现的稳健性。总之，本MR分析揭示了MMPs与肺栓塞之间潜在的因果关系，表明检测MMPs可能有助于识别肺栓塞高危人群，但仍需进一步研究。
