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

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

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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.

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