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Causal relationship between serum metalloproteinase 12 levels and aortic dissection and aortic aneurysm: a
Xiaoyan Feng1, Shoulei Chen1, Tao Liu1
1Department of Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Background:
Elevated matrix metalloproteinase-12 (MMP-12) levels have been shown to be elevated in patients with aortic dissection (AD) and aortic aneurysm (AA). However, whether MMP-12 is associated with AD and AA has not been conclusively examined. The aim of this study was to clarify the role of MMP-12 in AD and AA formation and to verify the correlation between MMP-12 and AD and AA development at the gene level via Mendelian randomization (MR) analysis.
Methods:
The data for analyzing MMP-12 gene mutations were obtained from the Integrative Epidemiology Unit (IEU) OpenGWAS database, which includes data from 21,758 European residents. Data on the genetic variation of AD and AA were retrieved from the FinnGen database. In the forward MR analysis, we evaluated the causal effect of MMP-12 on AD and AA. Subsequently, the causal association of AD and AA with MMP-12 was investigated in the reverse MR study. The inverse-variance weighting (IVW) method was the principal statistical technique used in this study.
Results:
In the forward MR analysis, the IVW results showed that serum MMP-12 levels were positively related to an increased risk of AD [odds ratio (OR) =1.301; 95% confidence interval (CI): 1.002-1.697; P=0.048] and AA (OR =1.121; 95% CI: 1.007-1.248; P=0.04). For the reverse MR studies, no genetic relationships were observed between AD or AA and MMP-12 levels, nor was any heterogeneity or pleiotropy.
Conclusions:
There was a correlation between serum MMP-12 and the risk of AD and AA. MMP-12 may be a potential therapeutic target for AD and AA.
Insights
Elevated matrix metalloproteinase-12 (MMP-12) is linked to increased risk of aortic dissection (AD) and aortic aneurysm (AA). This study used Mendelian randomization to confirm MMP-12 as a potential therapeutic target for these conditions.
Area of Science:
- Cardiovascular Genetics
- Proteomics
- Epidemiology
Background:
- Elevated matrix metalloproteinase-12 (MMP-12) levels are observed in patients with aortic dissection (AD) and aortic aneurysm (AA).
- The precise association between MMP-12 and the development of AD and AA requires further investigation.
- Understanding this relationship is crucial for identifying potential therapeutic targets.
Purpose of the Study:
- To clarify the role of MMP-12 in the formation of AD and AA.
- To verify the correlation between MMP-12 and AD/AA development at the genetic level using Mendelian randomization (MR) analysis.
Main Methods:
- Utilized the Integrative Epidemiology Unit (IEU) OpenGWAS database for MMP-12 genetic data (n=21,758 European residents).
- Retrieved genetic variation data for AD and AA from the FinnGen database.
- Employed forward and reverse Mendelian randomization analyses, primarily using the inverse-variance weighting (IVW) method.
Main Results:
- Forward MR analysis indicated a positive correlation between serum MMP-12 levels and increased risk of AD (OR=1.301, P=0.048) and AA (OR=1.121, P=0.04).
- Reverse MR studies found no significant genetic relationships between AD/AA and MMP-12 levels.
- No significant heterogeneity or pleiotropy was detected in the MR analyses.
Conclusions:
- A significant correlation exists between serum MMP-12 levels and the risk of developing AD and AA.
- MMP-12 emerges as a potential therapeutic target for managing AD and AA.
- Genetic evidence supports a causal link between MMP-12 and the pathogenesis of aortic diseases.
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