Feng Xiaoyan, Chen Shoulei, Liu Tao, Huang Hexi, Mariscalco Giovanni, Mestres Carlos A, Taylor Marcus, Nakamura Ken, Zheng Baoshi
Department of Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Cardiac Surgery, Glenfield Hospital, Leicester, UK.
J Thorac Dis. 2025 Apr 30;17(4):2377-2385. doi: 10.21037/jtd-2025-377. Epub 2025 Apr 27.
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.
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.
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.
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.
已有研究表明，主动脉夹层（AD）和主动脉瘤（AA）患者的基质金属蛋白酶12（MMP - 12）水平升高。然而，MMP - 12是否与AD和AA相关尚未得到最终证实。本研究旨在阐明MMP - 12在AD和AA形成中的作用，并通过孟德尔随机化（MR）分析在基因水平验证MMP - 12与AD和AA发展之间的相关性。
分析MMP - 12基因突变的数据来自综合流行病学单位（IEU）的OpenGWAS数据库，该数据库包含21,758名欧洲居民的数据。AD和AA基因变异的数据从芬兰基因数据库中获取。在前瞻性MR分析中，我们评估了MMP - 12对AD和AA的因果效应。随后，在反向MR研究中调查了AD和AA与MMP - 12的因果关联。逆方差加权（IVW）方法是本研究中使用的主要统计技术。
在前瞻性MR分析中，IVW结果显示血清MMP - 12水平与AD风险增加呈正相关[比值比（OR）= 1.301；95%置信区间（CI）：1.002 - 1.697；P = 0.048]和AA（OR = 1.121；95% CI：1.007 - 1.248；P = 0.04）。对于反向MR研究，未观察到AD或AA与MMP - 12水平之间的遗传关系，也没有任何异质性或多效性。
血清MMP - 12与AD和AA风险之间存在相关性。MMP - 12可能是AD和AA的潜在治疗靶点。
