The causal relationship between matrix metalloproteinase-3 and fibromyalgia: A two-sample Mendelian randomization analysis

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.