Related Experiment Video
Updated: Jan 17, 2026
Author Spotlight: Methodologies and Advancements of Chronic Pain Management Research
Published on: January 5, 2024
The causal relationship between matrix metalloproteinase-3 and fibromyalgia: A two-sample Mendelian randomization
Honglin Wang1,2, Hong Zhou3, Yifan Cai4
1Department of Orthopedics Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
Fibromyalgia is a chronic pain syndrome with incompletely understood pathogenesis. Matrix metalloproteinase-3 (MMP-3), a key enzyme involved in inflammation and tissue remodeling, has not been genetically validated for its causal relationship with fibromyalgia. This study aims to explore the causal association between MMP-3 and fibromyalgia using Mendelian randomization (MR) methods. Genome-wide association study (GWAS) data for MMP-3 levels (n = 21,758) were obtained from the IEU Open GWAS database, and GWAS data for fibromyalgia were extracted from public databases (n = 361,194). Inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode were used to evaluate causal effects. Heterogeneity tests, horizontal pleiotropy tests, and leave-one-out sensitivity analyses were performed to verify the robustness of the results. IVW analysis showed that per 1 standard deviation increase in MMP-3 level was associated with a 0.098% increase in fibromyalgia risk (odds ratio [OR] = 1.00098, 95% confidence interval = 1.00014-1.00182, P = .0225). MR-Egger (OR = 1.00050, P = .5183) and weighted median (OR = 1.00081, P = .0982) results were consistent with IVW but not statistically significant. Sensitivity analyses showed no significant heterogeneity (Cochran Q test, P > .05) or horizontal pleiotropy (MR-Egger intercept, P = .4391), and leave-one-out analysis indicated that individual single nucleotide polymorphisms did not affect the overall results. This study supports a potential causal association between MMP-3 and fibromyalgia through genetic evidence, suggesting that MMP-3 may be involved in the pathogenesis of fibromyalgia.
Insights
This study investigated the genetic link between matrix metalloproteinase-3 (MMP-3) and fibromyalgia. Findings suggest MMP-3 may play a causal role in fibromyalgia development, offering new insights into chronic pain syndrome pathogenesis.
Area of Science:
- Genetics
- Rheumatology
- Biochemistry
Background:
- Fibromyalgia is a chronic pain condition with unclear causes.
- Matrix metalloproteinase-3 (MMP-3) is implicated in inflammation and tissue remodeling.
- Genetic links between MMP-3 and fibromyalgia require validation.
Purpose of the Study:
- To explore the potential causal association between MMP-3 levels and fibromyalgia risk.
- To utilize Mendelian randomization (MR) methods for genetic evidence.
- To investigate MMP-3's role in fibromyalgia pathogenesis.
Main Methods:
- Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data.
- GWAS data for MMP-3 levels (n=21,758) and fibromyalgia (n=361,194).
- Inverse variance weighting (IVW), MR-Egger, and weighted median methods were employed.
Main Results:
- The IVW analysis indicated a potential causal link, with increased MMP-3 associated with higher fibromyalgia risk (OR=1.00098, P=0.0225).
- MR-Egger and weighted median analyses showed consistent trends but lacked statistical significance.
- Sensitivity analyses confirmed the robustness of the findings, with no significant heterogeneity or pleiotropy detected.
Conclusions:
- Genetic evidence supports a potential causal association between MMP-3 and fibromyalgia.
- MMP-3 may be involved in the underlying mechanisms of fibromyalgia.
- Further research into MMP-3 as a therapeutic target for fibromyalgia is warranted.
