Related Experiment Video
Updated: May 12, 2026
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
Causal association between matrix metalloproteinases and diabetic neuropathy: a two-sample Mendelian randomization
Chao Bai1,2, Wenwen Yang3, Guangwei Qi1
1Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Objective:
Diabetic neuropathy (DN), a common and debilitating complication of diabetes, significantly impairs the quality of life of affected individuals. While multiple studies have indicated changes in the expression of specific matrix metalloproteinases (MMPs) in patients with DN, and basic research has reported the impact of MMPs on DN, there is a lack of systematic research and the causal relationship remains unclear. The objective of this research is to investigate the casual relationship between MMPs and DN through two-sample Mendelian randomization (MR).
Methods:
Data for this investigation were derived from genome-wide association studies (GWAS) of MMPs and DN. For the analysis using two-sample MR, methods such as inverse variance weighted (IVW), weighted median, weighted mode, and MR-Egger were utilized, with IVW serving as the primary measure for determining causative impacts. To evaluate the analysis' heterogeneity and potential pleiotropy, sensitivity examinations including MR-PRESSO analysis, Cochran's Q test, and the leave-one-out test were conducted.
Results:
IVW analysis revealed that genetically decreased serum MMP-2 level were causally associated with a high risk of DN (OR = 0.88, 95% CI: 0.79-0.99, P = 0.026). Genetically elevated serum MMP-16 level were causally associated with a high risk of DN (OR = 1.15, 95% CI: 1.01-1.32, P = 0.038). Genetic prediction results showed no causal association between other MMPs (MMP14/17/9/12/7/3) and DN. Sensitivity analyses showed no significant heterogeneity or pleiotropy.
Conclusion:
In summary, this research uncovered a genetic causal relationship between heightened MMP-16 levels and reduced MMP-2 concentrations, and DN risk. These discoveries offer new perspectives on the role of MMPs in DN etiology and establish a foundational premise for further investigations into MMP-targeted therapeutic interventions.
Insights
Matrix metalloproteinases (MMPs) play a role in diabetic neuropathy (DN). Lower MMP-2 levels and higher MMP-16 levels are causally linked to increased DN risk, suggesting new therapeutic targets.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Diabetic neuropathy (DN) is a severe complication of diabetes, impacting patient quality of life.
- While matrix metalloproteinases (MMPs) are implicated in DN, their precise causal role remains unclear.
- Existing research lacks systematic investigation into the MMP-DN causal link.
Purpose of the Study:
- To investigate the causal relationship between matrix metalloproteinases (MMPs) and diabetic neuropathy (DN).
- Utilize two-sample Mendelian randomization (MR) to explore genetic associations.
Main Methods:
- Employed two-sample Mendelian randomization (MR) using genome-wide association study (GWAS) data for MMPs and DN.
- Applied inverse variance weighted (IVW), weighted median, and MR-Egger methods.
- Conducted sensitivity analyses (MR-PRESSO, Cochran's Q, leave-one-out) to assess heterogeneity and pleiotropy.
Main Results:
- Genetically decreased serum MMP-2 levels were associated with a higher risk of DN (OR=0.88, P=0.026).
- Genetically elevated serum MMP-16 levels were associated with a higher risk of DN (OR=1.15, P=0.038).
- No significant causal associations were found for other tested MMPs (MMP14/17/9/12/7/3) with DN.
Conclusions:
- Established a genetic causal link between MMP-16 and MMP-2 levels and diabetic neuropathy risk.
- Findings provide novel insights into MMPs' role in DN pathogenesis.
- Suggests potential for MMP-targeted therapies for diabetic neuropathy.
