Liu Wenkai, Guo Licheng, Zhang Yongfa, He Wubing
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.
Medicine (Baltimore). 2025 Jan 31;104(5):e41373. doi: 10.1097/MD.0000000000041373.
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.
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。