Proteome-wide Mendelian randomization study of plasma proteins associated with mastitis and prediction of potential candidates from herbal medicine
Clinical Traditional Medicine and Pharmacology, 2025
Zhang S., Ren J., Liu B., Wang M., Huang L., Mao Y., Xie X., Qian Y.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases | Pathophysiology | Plasma |  Olink Explore 3072/384 |
Abstract
Background
Previous epidemiological studies have reported inconsistent associations of plasma protein levels with risk of mastitis. Therefore, it is necessary to explore their exact relationship and identify drug candidates from traditional Chinese medicines (TCM).
Objective
To explore circulating levels of proteins that are associated with the risk of mastitis, and to identify TCMs that target these dysregulated proteins for potential therapeutic applications in mastitis.
Methods
Genetic instruments for plasma proteome were derived from a UK Biobank genome-wide association study (GWAS) (n = 54,219). Mastitis data were obtained from FinnGen (2,468 cases; 258,508 controls). Potential causal associations were assessed via inverse variance weighted (IVW) Mendelian randomization, with several sensitivity analyses. Results were further replicated using data from an Icelandic GWAS (n = 35,559). Protein-targeted components by TCMs were retrieved from the TCMID database and cross-validated against clinical therapies.
Results
Genetically predicted circulating levels of 99 plasma proteins showed suggestive associations with mastitis risk in our analysis. Sixteen proteins were replicated, with Toll-like receptor 3 demonstrating the strongest protective effect (OR: 0.80, 95% CI: 0.71–0.91; P = 3.75 × 10–4). CD59 was also found to be associated with an increased risk of mastitis (OR: 1.37, 95% CI: 1.10–1.72; P = 0.005). Totally, 24 TCMs (such as Yiyiren, Zhizi, Dangshen, and Fuling) were found to target these proteins, which was aligned with approved mastitis treatments. Enrichment analyses further highlighted the role of inflammation and leukocyte-mediated immunity in the pathogenesis of mastitis.
Conclusion
Toll-like receptor 3 may serve as a novel biomarker and potential therapeutic target for mastitis. Experimental studies are needed to elucidate mechanisms of TLR3 and the effects of corresponding predicted TCMs on mastitis.