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Plasma Proteins and Genes Associated with Protein and Risks for Diabetic Foot Diseases Identified Using Multi- Ornics
Man Fang1,2, Yitian Lei3, Pengju Fan4
1State Key Laboratory of Powder Metallurgy, Central South University, Changsha, 410083, China.
Current Medicinal Chemistry
|July 28, 2026
Summary
This study identifies key plasma proteins and genes linked to diabetic foot diseases (DFD). These findings offer new targets for developing effective therapies to manage DFD and improve patient quality of life.
Area of Science:
- Genetics and Omics
- Biomarker Discovery
- Precision Medicine
Background:
- Diabetic foot diseases (DFD) significantly reduce quality of life.
- Limited understanding of DFD biomarkers and therapies necessitates identifying causal molecular targets.
Purpose of the Study:
- To screen for therapeutic targets for DFD using integrated multi-omics data and Mendelian randomization (MR).
- To identify causal molecular mechanisms underlying DFD for precision medicine strategies.
Main Methods:
- Integrated plasma proteome and genome-wide data with MR.
- Utilized genetic instruments (pQTLs/e-QTLs) to proxy protein and gene expression levels.
- Analyzed causal effects on DFD outcomes (atherosclerosis, neuropathy, Charcot foot) using MR methods, followed by functional enrichment and colocalization analyses.
Main Results:
- Identified protective plasma proteins (EPOR, MICA, PRKCG) and a risk protein (TXNDC15) for DFD.
- Revealed 42 blood-expressed genes with significant causal effects on DFD-related traits, enriched in immune-inflammatory pathways.
- Confirmed shared causal variants for DFD outcomes using colocalization analysis.
Conclusions:
- Established a novel framework for DFD mechanisms via multi-omics and MR integration.
- Highlighted EPOR, PRKCG, MICA, and TXNDC15 plasma proteins and 42 genes as causal contributors to DFD.
- Bridged genetic insights with potential precision medicine strategies for DFD management, pending further validation.
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