Matrix Metalloproteinase and Aortic Aneurysm: A Two-sample Mendelian Randomization Study

Abstract

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.