Causal association between matrix metalloproteinases and gout: A two-sample mendelian randomization study.

BACKGROUND

Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of gout. However, the causal nature of their associations remains unclear. This study aimed to evaluate the potential causal effects of MMPs on gout.

METHODS

The study was performed using two-sample Mendelian randomization (MR) analyses with publicly available genome-wide association study (GWAS) summary statistics of ten MMP types and gout. Four complementary MR methods were employed, with Inverse-variance weighted (IVW) analysis as the primary approach, supplemented by MR-Egger, weighted median, and weighted mode. The robustness of the causal estimates was further evaluated through sensitivity analyses, including MR-Egger intercept, Cochran's Q test, leave-one-out (LOO) analysis, and the MR pleiotropy residual sum and outlier (MR-PRESSO) test.

RESULTS

Genetically predicted MMPs showed no evidence of a causal effect on gout. In particular, previously reported candidates such as MMP3 and MMP9 demonstrated no significant associations (MMP3: OR = 0.993, 95 % CI: 0.955 - 1.033, P = 0.739; MMP9: OR = 0.974, 95 %CI: 0.928 - 1.022, P = 0.278). Results from MR-Egger, weighted median, and weight mode analyses were consistent with those of IVW. No substantial heterogeneity or horizontal pleiotropy was observed across analyses.

CONCLUSIONS

This two-sample MR study provides no evidence supporting a causal relationship between MMPs and gout. Further research is warranted to clarify their potential roles and underlying biological mechanisms.