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Author Spotlight: Evaluating Traditional Chinese Therapy for Ankylosing Spondylitis in Mice
Published on: October 27, 2023
The causal effect of matrix metalloproteinase-3 on ankylosing spondylitis: Evidence from Mendelian randomization
Wenkai Liu1,2, Licheng Guo1,2, Yongfa Zhang1,2
1Department of Emergency, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian, China.
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.
Insights
Matrix metalloproteinase-3 (MMP-3) plays a causal role in ankylosing spondylitis (AS). This Mendelian randomization study confirms MMP-3
Area of Science:
- Genetics
- Immunology
- Rheumatology
Background:
- Observational studies suggest matrix metalloproteinase-3 (MMP-3) may benefit ankylosing spondylitis (AS).
- The causal relationship between MMP-3 and AS remains uncertain.
- Understanding this link is crucial for AS pathogenesis and treatment.
Purpose of the Study:
- To investigate the causal relationship between MMP-3 and AS using Mendelian randomization.
- To leverage large-scale genome-wide association study data for robust analysis.
- To provide evidence for MMP-3's role in AS development.
Main Methods:
- Mendelian randomization (MR) analysis utilizing genome-wide association studies (GWAS) data.
- GWAS data for MMP-3 (n=21,758) and AS (n=297,932) from public repositories.
- Employing multiple MR methods including IVW, weighted median, weighted mode, and MR-Egger.
- Sensitivity analyses using Cochran Q, MR-PRESSO, and MR-Egger intercept to assess heterogeneity and pleiotropy.
Main Results:
- The inverse-variance weighted (IVW) method indicated a causal effect of MMP-3 on AS (OR=0.9047, P=0.0823).
- Concordant results were observed across other MR methods (P < .05).
- Sensitivity analyses confirmed the reliability and robustness of the findings.
Conclusions:
- This MR study provides strong evidence for a causal role of MMP-3 in the development of ankylosing spondylitis.
- The findings offer valuable insights into the underlying mechanisms of AS.
- MMP-3 emerges as a potential therapeutic target for ankylosing spondylitis.
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