Causal Relationship Between Serum Zinc Levels and Diabetic Kidney Disease (DKD): A Plasma Proteomics Mediation Study
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View abstract on PubMed
Summary
This summary is machine-generated.Lower serum zinc levels increase the risk of diabetic kidney disease (DKD). This study used Mendelian randomization to identify 26 mediating plasma proteins and four pathways, revealing mechanisms behind zinc
Area Of Science
- Nephrology and Endocrinology
- Genetics and Bioinformatics
Background
- Serum zinc deficiency is linked to diabetic kidney disease (DKD) progression.
- Zinc supplementation may mitigate DKD-related kidney damage.
- The causal relationship and underlying mechanisms between serum zinc and DKD remain unclear.
Purpose Of The Study
- To investigate the causal effect of serum zinc levels on DKD incidence using a two-sample Mendelian randomization (MR) approach.
- To identify mediating plasma proteins and pathways involved in the association between serum zinc and DKD.
- To elucidate the mechanistic link between low serum zinc and DKD development.
Main Methods
- Two-sample Mendelian randomization (MR) study utilizing single nucleotide polymorphisms (SNPs) as instrumental variables.
- Inverse variance weighting (IVW) and MR-Egger regression for causal inference, with sensitivity analyses.
- Pathway MR analysis incorporating plasma proteomics and subsequent metabolic/signaling pathway enrichment analysis.
Main Results
- Lower serum zinc levels were causally associated with an increased risk of DKD (OR: 0.886; p < 0.001).
- Twenty-six plasma proteins, including N-terminal Xaa-Pro-Lys N-methyltransferase 1 and Multiple PDZ domain protein, were identified as mediators.
- Mediation effects ranged from 3.31% to 22.06%, involving pathways like Digestion and DSCAM interactions.
Conclusions
- Low serum zinc is a causal risk factor for diabetic kidney disease.
- Specific plasma proteins and metabolic/signaling pathways mediate the detrimental effects of low zinc on kidney health.
- Findings provide mechanistic insights and a basis for therapeutic strategies targeting zinc levels in DKD.
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