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血清金属蛋白酶12水平与大动脉剖析和大动脉动脉瘤之间的因果关系:双向的门德尔随机化研究

Xiaoyan Feng¹, Shoulei Chen¹, Tao Liu¹

¹Department of Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Journal of thoracic disease

|May 22, 2025

概括

升高的矩阵金属蛋白酶-12 (MMP-12) 与大动脉解剖 (AD) 和大动脉动脉瘤 (AA) 的风险增加有关. 这项研究使用了门德尔的随机化来确认MMP-12作为这些疾病的潜在治疗点.

科学领域:

心血管遗传学心血管遗传学
蛋白质组学是指蛋白质组学.
流行病学流行病学

背景情况:

在患有大动脉剖析 (AD) 和大动脉动脉瘤 (AA) 的患者中观察到升高的矩阵金属蛋白酶-12 (MMP-12) 水平.
MMP-12与AD和AA的发展之间的准确关联需要进一步调查.
了解这种关系对于确定潜在的治疗点至关重要.

研究的目的:

澄清MMP-12在AD和AA形成中的作用.
通过使用孟德尔随机化 (MR) 分析,在遗传层面验证MMP-12和AD/AA发育之间的相关性.

主要方法:

使用综合流行病学单位 (IEU) OpenGWAS数据库获取MMP-12遗传数据 (n=21,758名欧洲居民).
从FinnGen数据库中检索了AD和AA的遗传变异数据.
采用前向和反向的门德尔随机化分析,主要使用反变量加权 (IVW) 方法.

主要成果:

前进的MR分析表明,血清MMP-12水平与AD (OR=1.301,P=0.048) 和AA (OR=1.121,P=0.04) 的风险增加之间存在正相关性.
反向MR研究发现AD/AA和MMP-12水平之间没有显著的遗传关系.
在MR分析中没有检测到显著的异质性或性.

结论:

血清MMP-12水平与发展AD和AA的风险之间存在显著的相关性.
MMP-12成为管理AD和AA的潜在治疗标.
遗传证据支持MMP-12与大动脉疾病的发病之间存在因果关系.

关键词:

矩阵金属蛋白酶-12 (MMP-12) 是一种门德尔的随机化 (MR)大动脉动脉瘤 (AA)大动脉剖析 (AD)

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