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Causal association between matrix metalloproteinases and gout: A two-sample mendelian randomization study
Da-Wei Chen1, Gaohua Hu2, Li Mao3
1Department of Cardiology, Qichun County People's Hospital, Huanggang, China.
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.
Insights
This study found no evidence that matrix metalloproteinases (MMPs) causally affect gout. Further research is needed to understand the relationship between MMPs and gout pathogenesis.
Area of Science:
- Genetics
- Rheumatology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are linked to gout pathogenesis.
- The causal role of MMPs in gout remains undetermined.
Purpose of the Study:
- To investigate the potential causal effects of matrix metalloproteinases (MMPs) on gout development.
Main Methods:
- Two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data for ten MMPs and gout.
- Employed Inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode methods.
- Conducted sensitivity analyses including MR-Egger intercept, Cochran's Q test, leave-one-out, and MR-PRESSO.
Main Results:
- No genetic evidence supported a causal effect of MMPs on gout.
- Specific MMPs, including MMP3 and MMP9, showed no significant association with gout risk.
- Sensitivity analyses confirmed the robustness of findings, with no significant heterogeneity or pleiotropy.
Conclusions:
- This MR study found no causal link between MMPs and gout.
- Further investigation is required to elucidate the precise roles and mechanisms of MMPs in gout.
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