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Published on: March 8, 2019
Matrix Metalloproteinase and Aortic Aneurysm: A Two-sample Mendelian Randomization Study
Tao Qin1, Jiankai Zhong2, Pinglan Li1
1Department of Ultrasound, Shunde Hospital, Southern Medical University, (The First People's Hospital of Shunde Foshan), Foshan, China.
Background:
Studies have linked matrix metalloproteinases (MMPs) to both thoracic aortic aneurysm and abdominal aortic aneurysm (TAA and AAA). The precise MMPs entailed in this procedure, however, were still unknown. This study used a two-sample Mendelian randomization (MR) analysis to look into the causal relationship between MMPs and the risk of TAA and AAA.
Methods:
Eight MMPs, including MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-12, and MMP-13, were found among people of European ancestry with accessible Genome-Wide Association Studies (GWAS). We employed the findings from Genome-Wide Association Studies (GWAS) for 8 MMPs, and TAA and AAA from the FinnGen consortiums (3,201 cases and 317,899 controls, respectively) were used in a two-sample MR analysis. The primary method of analysis for MR was the inverse variance weighted (IVW) method, along with analyses of heterogeneity and horizontal pleiotropy. 31 single-nucleotide polymorphisms connected to MMP were retrieved.
Results:
IVW demonstrated a negative causal association between TAA and AAA and serum MMP-12 levels. The incidence of TAA decreased by 1.031% for every 1 ng/mL increase in serum MMP-12 [odds ratio (OR) = 0.897, 95% confidence interval (CI): 0.831-0.968, P = 0.005]. The incidence of AAA fell by 1.653% (OR = 0.835, 95% CI: 0.752-0.926, P = 0.001) for every 1 ng/mL increase in serum MMP-12. There was no horizontal pleiotropy or heterogeneity in the MR data (P > 0.05).
Conclusions:
The levels of TAA and AAA and serum MMP-12 are causally related. MMP-12 is a factor that reduces the risk of AAA and TTA. Our study suggested that MMP-12 level is causally associated with a decreased risk of TAA and AAA.
Insights
Matrix metalloproteinase-12 (MMP-12) is causally linked to reduced risks of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA). Higher MMP-12 serum levels are associated with decreased TAA and AAA incidence, suggesting a protective role.
Area of Science:
- Genetics
- Cardiovascular Science
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are implicated in thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA).
- Specific MMPs involved in aneurysm development remain unclear.
- Mendelian randomization (MR) is a valuable tool for investigating causal relationships.
Purpose of the Study:
- To investigate the causal relationship between specific matrix metalloproteinases (MMPs) and the risk of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA).
- To identify potential therapeutic targets for aneurysm prevention and treatment.
Main Methods:
- A two-sample Mendelian randomization (MR) analysis was conducted using Genome-Wide Association Studies (GWAS) data.
- Eight MMPs (MMP-1, -2, -3, -8, -9, -10, -12, -13) and TAA/AAA data from the FinnGen consortium were analyzed.
- The inverse variance weighted (IVW) method was the primary analytical approach, with assessments for heterogeneity and horizontal pleiotropy.
Main Results:
- A significant inverse causal association was found between serum MMP-12 levels and both TAA and AAA.
- Increased MMP-12 levels correlated with a reduced incidence of TAA (OR=0.897, P=0.005) and AAA (OR=0.835, P=0.001).
- No significant heterogeneity or horizontal pleiotropy was detected in the MR analysis.
Conclusions:
- Serum MMP-12 levels are causally associated with a reduced risk of TAA and AAA.
- MMP-12 demonstrates a protective effect against the development of both thoracic and abdominal aortic aneurysms.
- Targeting MMP-12 may represent a novel therapeutic strategy for aneurysm disease.
