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

Abstract

BackgroundStudies have linked matrix metalloproteinases (MMPs) to both abdominal and thoracic aortic aneurysms (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 AA.MMP and aortic aneurysm MethodsEight 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 eight 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 method (IVW), along with analyses of heterogeneity and horizontal pleiotropy. 31 SNPs connected to MMP were retrieved. ResultsIVW demonstrated a negative causal association between TAA and AAA and serum MMP-12 levels. The incidence of TAA decreased by 1.031% for every 1ng/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 1ng/mL increase in serum MMP-12. There was no horizontal pleiotropy or heterogeneity in the MR data (P > 0.05). ConclusionThe 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.