Association of urinary copper and gestational diabetes mellitus: role of epigenome-wide DNA methylation and proteomics
The Journal of Clinical Endocrinology & Metabolism, 2025
Li Y., Zhang S., Lai Y., Wu P., Sun F., Jiao A., He X., Yang Y., Yuan J., Wu N., Li R., Dong Y., Wang T., Li F., Li S., Liu G., Hu Y., Chen D., Wu J., Pan A., Pan X.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Metabolic Diseases Environmental Toxicology | Pathophysiology | Serum |  Olink Explore 3072/384 |
Abstract
Context
The association between copper exposure and gestational diabetes mellitus (GDM) remains inconclusive.
Objectives
Our study aimed to investigate the prospective relationship between urinary copper and GDM and the mediating role of DNA methylation for this association.
Design
Nested case-control study based on the Tongjing-Huaxi-Shuangliu Birth Cohort.
Participants, exposure and main outcome measures
Urinary copper and genome-wide DNA methylations were measured in early pregnancy for 432 pregnant women, and 737 proteins were measured in a subset of 150 pregnant women.
Results
Urinary copper levels were positively associated with risk of GDM (adjusted odd ratio =1.48 for each one-unit increase in the log-transformed levels of copper, 95% confidence interval 1.15-1.91). 73 differential cytosine-phosphoguanine sites (CpGs) were identified to associate with copper. Of these CpGs, cg23773809 annotated to SNX10 mediated 24.7% and 22.4% of the copper-GDM and copper-1 h plasma glucose (1-h PG) association, respectively. cg04168577 annotated to PPFIBP2 and cg06105935 mediated 23.4% and 13.9% of the copper-1-h PG association, respectively. The protein, CD2AP was found to be a reliable predictor for GDM. The 73 differential CpGs mediated 64.1% of the copper-CD2AP association.
Conclusions
Copper exposure may induce alterations in DNA methylation patterns, which can subsequently lead to changes in the expression of proteins associated with GDM and elevate the risk of developing GDM.