Department of Ultrasound, Shunde Hospital, Southern Medical University, (The First People's Hospital of Shunde Foshan), Foshan, China.
Department of Cardiology, Shunde Hospital, Southern Medical University, (The First People's Hospital of Shunde Foshan), Foshan, China.
Ann Vasc Surg. 2024 Aug;105:227-235. doi: 10.1016/j.avsg.2024.02.011. Epub 2024 Apr 10.
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.
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.
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).
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.
研究表明基质金属蛋白酶(MMPs)与胸主动脉瘤和腹主动脉瘤(TAA 和 AAA)均有关联。然而,这一过程中具体涉及到哪些 MMPs 仍不得而知。本研究采用两样本 Mendelian 随机化(MR)分析,探究 MMPs 与 TAA 和 AAA 发病风险之间的因果关系。
在欧洲血统人群中,我们发现了 8 种 MMPs(MMP-1、MMP-2、MMP-3、MMP-8、MMP-9、MMP-10、MMP-12 和 MMP-13),这些 MMPs 均与可获取的全基因组关联研究(GWAS)相关。我们利用全基因组关联研究(GWAS)的结果来分析 8 种 MMPs,以及 FinnGen 联合会(分别有 3201 例病例和 317899 例对照)的 TAA 和 AAA 数据,进行两样本 MR 分析。MR 的主要分析方法是逆方差加权(IVW)法,并对异质性和水平多效性进行分析。我们共检索到 31 个与 MMP 相关的单核苷酸多态性。
IVW 表明 TAA 和 AAA 与血清 MMP-12 水平之间存在负向因果关系。血清 MMP-12 每增加 1ng/ml,TAA 的发病风险降低 1.031%[比值比(OR)=0.897,95%置信区间(CI):0.831-0.968,P=0.005]。血清 MMP-12 每增加 1ng/ml,AAA 的发病风险降低 1.653%(OR=0.835,95% CI:0.752-0.926,P=0.001)。MR 数据不存在水平多效性或异质性(P>0.05)。
TAA 和 AAA 以及血清 MMP-12 水平之间存在因果关系。MMP-12 是降低 AAA 和 TTA 发病风险的因素。本研究表明 MMP-12 水平与 TAA 和 AAA 发病风险降低有关。