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Causal relationship between matrix metalloproteinase and pulmonary embolism: a bidirectional two-sample Mendelian
1Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, No. 215, Heping West Road, Shijiazhuang, 050000, Hebei Province, China.
Scientific Reports
|January 2, 2025
Summary
This study investigated matrix metalloproteinases (MMPs) and pulmonary embolism risk. Elevated pulmonary embolism risk was linked to MMP19, while MMP12 showed a potential reduced risk, suggesting MMPs may aid in identifying high-risk individuals.
Area of Science:
- Genetics and Bioinformatics
- Cardiovascular Research
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are implicated in various physiological and pathological processes.
- Pulmonary embolism (PE) is a significant cause of morbidity and mortality.
- Understanding the genetic links between MMPs and PE is crucial for risk stratification.
Purpose of the Study:
- To evaluate the potential causal relationship between matrix metalloproteinases (MMPs) and pulmonary embolism (PE) using Mendelian randomization.
- To identify specific MMPs that may influence PE risk.
- To explore the potential of MMPs as biomarkers for PE risk assessment.
Main Methods:
- Mendelian randomization (MR) analysis utilizing genome-wide association study (GWAS) data for PE (UK Biobank) and MMPs (Icelandic cohort).
- Employed instrumental variable analysis (IVW) and weighted median methods for primary analysis.
- Conducted sensitivity analyses including MR-Egger, MR-PRESSO, Cochran's Q, and leave-one-out to ensure result robustness.
Main Results:
- Mendelian randomization analysis indicated an elevated risk of pulmonary embolism associated with MMP19 (OR=1.0009, P=0.041).
- Weighted median analysis suggested a reduced risk of pulmonary embolism related to MMP12 (OR=0.9992, P=0.038), despite non-significant IVW results.
- No significant causal associations were found for other tested MMPs (MMP1, MMP2, MMP3, MMP7-10, MMP13, MMP14, MMP16, MMP17, MMP20) with pulmonary embolism.
Conclusions:
- This MR study suggests a potential causal link between specific MMPs and pulmonary embolism.
- MMP19 and MMP12 warrant further investigation for their roles in PE pathogenesis and as potential risk biomarkers.
- Additional research is necessary to confirm these findings and explore therapeutic implications.
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