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Causal relationship between matrix metalloproteinase and pulmonary embolism: a bidirectional two-sample Mendelian

Xiaowei Gong1, Yadong Yuan2

  • 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
PubMed

Insights

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.
Keywords:
CausalityGenome-wide association studyMatrix metalloproteinaseMendelian randomizationPulmonary embolism

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