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Causal Association of Galectins and Diabetic Retinopathy: A Two-Sample Mendelian Randomization Study.
Shanshan Yang1, Cong Zheng1, Qianyin Zheng1
1Department of Ophthalmology, Taizhou Municipal Hospital (Taizhou University Affiliated Municipal Hospital), School of Medicine, Taizhou University, Taizhou, Zhejiang, China.
Current Eye Research
|June 18, 2025
Summary
This study reveals that higher Galectin-4 (Gal-4) levels increase the risk of diabetic retinopathy (DR) and proliferative DR (PDR). Galectin-3 (Gal-3) and Galectin-3 binding protein are linked to severe non-proliferative DR (SNPDR), while Galectin-9 (Gal-9) shows a decreased risk.
Area of Science:
- Genetics and Ophthalmology
- Biomarkers and Disease Risk
- Mendelian Randomization Studies
Background:
- Diabetic retinopathy (DR) is a significant microvascular complication of diabetes, affecting vision.
- Observational studies suggest an association between Galectins (Gal) and DR risk, but causality remains uncertain.
- Understanding the causal link between specific Galectins and DR phenotypes is crucial for targeted interventions.
Purpose of the Study:
- To investigate the causal associations between circulating galectin family levels and the risk of diabetic retinopathy (DR).
- To explore the causal relationships between galectins and specific DR phenotypes: proliferative DR (PDR), background DR (BDR), and severe non-proliferative background DR (SNPDR).
- To employ two-sample Mendelian randomization (MR) analysis for robust causal inference.
Main Methods:
- Utilized single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) as instrumental variables (IVs).
- Selected qualified SNPs associated with galectins through a rigorous screening process.
- Performed Mendelian randomization analysis, primarily using the Inverse Variance Weighted (IVW) method, to assess causal effects, presenting results as odds ratios (OR) with 95% confidence intervals (CI).
Main Results:
- Galectin-4 (Gal-4) levels showed a causal relationship with an elevated risk of DR (OR=1.068) and PDR (OR=1.084).
- Galectin-3 (Gal-3) demonstrated a causal effect on the risk of severe non-proliferative DR (SNPDR) (OR=1.455).
- Galectin-3 binding protein was causally associated with higher SNPDR risk (OR=1.295), while Galectin-9 (Gal-9) was associated with decreased SNPDR risk (OR=0.669).
Conclusions:
- Galectin-4 (Gal-4) levels are causally linked to increased risks of diabetic retinopathy (DR) and proliferative DR (PDR).
- Galectin-3 (Gal-3) and Galectin-3 binding protein causally contribute to the risk of severe non-proliferative DR (SNPDR).
- Galectin-9 (Gal-9) exhibits a causal association with a decreased risk of severe non-proliferative DR (SNPDR).
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