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基质金属蛋白酶-3对强直性脊柱炎的因果效应:来自孟德尔随机化的证据。

The causal effect of matrix metalloproteinase-3 on ankylosing spondylitis: Evidence from Mendelian randomization.

作者信息

Liu Wenkai, Guo Licheng, Zhang Yongfa, He Wubing

机构信息

Department of Emergency, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian, China.

Department of Emergency, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, China.

出版信息

Medicine (Baltimore). 2025 Jan 31;104(5):e41373. doi: 10.1097/MD.0000000000041373.

DOI:10.1097/MD.0000000000041373
PMID:39889180
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11789851/
Abstract

Previous investigations through observation have found that matrix metalloproteinase-3 (MMP-3) has benefits for ankylosing spondylitis (AS) but it is uncertain whether there is a true positive causal connection. Our goal was to demonstrate the relationship between AS and MMP-3. We executed Mendelian randomization (MR) research utilizing genome-wide association studies genetic data (n = 21,758) for MMP-3 publicly available from IEU Open and genome-wide association studies data for AS (n = 297,932) from FinnGen Biobank. The specific MR protocols were weighted median, weighted mode, MR-Egger, and inverse-variance weighted (IVW). Subsequently, the Cochran Q evaluate, MR pleiotropy residual sum and outlier, and MR-Egger intercept were used to evaluate the heterogeneity and multiplicative effects of instrumental variables. The IVW method demonstrated that MMP-3 had a causal effect on AS (odds ratio, 0.9047 [95% confidence interval, 0.8080-1.0129]; P = .0823). Certainly, other MR techniques were in accordance with the tendency of the IVW method (P < .05), and sensitivity testing verified the reliability of this MR result. This MR study substantiates the causal role of MMP-3 in the development of AS, offering valuable insights into the disease mechanism and potential therapeutic targets.

摘要

以往通过观察性研究发现,基质金属蛋白酶-3(MMP-3)对强直性脊柱炎(AS)有益,但尚不确定是否存在真正的正向因果关系。我们的目标是证明AS与MMP-3之间的关系。我们利用IEU Open公开提供的MMP-3全基因组关联研究遗传数据(n = 21,758)和FinnGen生物银行的AS全基因组关联研究数据(n = 297,932)进行孟德尔随机化(MR)研究。具体的MR方案包括加权中位数、加权模式、MR-Egger和逆方差加权(IVW)。随后,使用Cochran Q评估、MR多效性残差和异常值以及MR-Egger截距来评估工具变量的异质性和乘性效应。IVW方法表明MMP-3对AS有因果效应(优势比,0.9047 [95%置信区间,0.8080 - 1.0129];P = 0.0823)。当然,其他MR技术与IVW方法的趋势一致(P < 0.05),敏感性测试验证了该MR结果的可靠性。这项MR研究证实了MMP-3在AS发病中的因果作用,为疾病机制和潜在治疗靶点提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f36/11789851/aad9205b75f9/medi-104-e41373-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f36/11789851/7440d847b96d/medi-104-e41373-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f36/11789851/465563bc3976/medi-104-e41373-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f36/11789851/b8c3138781e6/medi-104-e41373-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f36/11789851/aad9205b75f9/medi-104-e41373-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f36/11789851/7440d847b96d/medi-104-e41373-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f36/11789851/465563bc3976/medi-104-e41373-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f36/11789851/b8c3138781e6/medi-104-e41373-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f36/11789851/aad9205b75f9/medi-104-e41373-g004.jpg

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Front Immunol. 2023 May 25;14:1175421. doi: 10.3389/fimmu.2023.1175421. eCollection 2023.
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Insights into modifiable risk factors of erectile dysfunction, a wide-angled Mendelian Randomization study.
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Matrix metalloproteinase-3 (MMP-3)-mediated gene therapy for glaucoma.基质金属蛋白酶-3(MMP-3)介导的青光眼基因治疗。
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Evaluating the Causal Effects of TIMP-3 on Ischaemic Stroke and Intracerebral Haemorrhage: A Mendelian Randomization Study.评估基质金属蛋白酶组织抑制因子-3对缺血性卒中和脑出血的因果效应:一项孟德尔随机化研究。
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