Causal relationship between matrix metalloproteinases and diabetic retinopathy: A bidirectional two-sample Mendelian...

Area of Science:

• Ophthalmology
• Genetics
• Biochemistry

Background:

• Matrix metalloproteinases (MMPs) are implicated in diabetic retinopathy (DR) pathogenesis.
• The precise causal links between specific MMPs and DR risk remain unclear.
• Further investigation is needed to elucidate the role of MMPs in DR development.

Purpose of the Study:

• To investigate the potential causal effects of various MMPs on the risk of developing diabetic retinopathy (DR).
• To explore the bidirectional relationship between MMPs and DR using Mendelian randomization.
• To identify specific MMPs that may influence DR risk or progression.

Main Methods:

• Bidirectional two-sample Mendelian randomization (MR) analyses were employed.
• Inverse variance weighted (IVW) method was the primary analytical approach.
• Sensitivity analyses were conducted to ensure the robustness of the findings.

Main Results:

• Genetically predicted MMP-7 levels were associated with an increased risk of DR (OR=1.15).
• Genetically predicted MMP-8 levels were robustly associated with a reduced risk of DR (OR=0.86).
• No significant causal associations were found for other MMPs or in the reverse MR analysis.

Conclusions:

• MMP-7 may contribute to an increased risk of DR.
• MMP-8 may exert a protective effect against DR.
• These findings suggest specific MMPs have distinct roles in DR pathophysiology, warranting further mechanistic studies.