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Original article Causal effect of serum matrix metalloproteinase levels on venous thromboembolism: a Mendelian randomization study
Deheng Hanorcid , Fangcong Yuorcid , Liangrong Zhengorcid
Epidemiol Health 2024;e2024046
DOI: https://doi.org/10.4178/epih.e2024046 [Accepted]
Published online: April 24, 2024
The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, China
Corresponding author:  Liangrong Zheng,
Email: 1191066@zju.edu.cn
Received: 6 March 2024   • Revised: 26 March 2024   • Accepted: 7 April 2024
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OBJECTIVES
Serum matrix metalloproteinase (MMP) levels are associated with cardiovascular diseases. However, the causal associations between serum levels of specific MMPs and venous thromboembolism (VTE) remain unclear. The present study sought to explore the causal relationship between serum MMP levels and VTE by using the Mendelian randomization (MR) method.
METHODS
In this study 2-sample MR study, the exposure data on serum MMP levels were derived from genome-wide association studies involving 21,758 individuals from 13 cohorts of European descent. The outcome data on VTE, including deep vein thrombosis and pulmonary embolism, were derived from the FinnGen research project. The primary method used was the inverse-variance weighting method. The MR-Egger intercept test and the Cochran Q test were used to evaluate pleiotropy and heterogeneity.
RESULTS
Using the inverse-variance weighting method, higher serum MMP-12 levels were found to be associated with an increased risk of VTE (odds ratio, 1.04; 95% confidence interval, 1.01–1.07; p=0.0015). Moreover, there was a weak association between the levels of certain MMPs and VTE. Sensitivity analyses revealed no significant heterogeneity and pleiotropy in our study, and the Steiger directionality test did not reveal a significant reverse causation association.
CONCLUSIONS
There is a causal association between MMP-12 levels and VTE, which may have substantial implications for the diagnostic and therapeutic strategies used for VTE.


Epidemiol Health : Epidemiology and Health