Causal association between matrix metalloproteinases and diabetic neuropathy: a two-sample Mendelian randomization...

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.