Associations of heavy metals and essential trace elements exposures with rheumatoid arthritis: The potential mediating role of telomere length.

Abstract

The relationships linking heavy metals and essential trace elements to rheumatoid arthritis (RA) risk have not been fully elucidated. The aim of this study was to explore the relationship between multi-metal exposure and the risk of RA, and to assess the mediating role of telomere length (TL) in these associations.This case-control study recruited 548 RA patients and 548 controls, quantifying peripheral blood concentrations of 15 metals (Cr, Mn, Co, Zn, Se, Sr, Mo, Sn, Sb, Cu, Ni, Cd, Ba, Tl, Pb) via inductively coupled plasma mass spectrometry (ICP-MS). Associations between metals and RA were assessed using logistic regression, quantile-based g-computation (qgcomp), and Bayesian kernel machine regression (BKMR). Overall concentrations of five heavy metals (Cu, Pb, Ni, Cd, and Ba) were positively associated with RA risk, primarily driven by exposures to Cu, Ni, and Cd. Conversely, overall concentrations of seven essential metals (Sn, Se, Mn, Cr, Zn, Sr, and Mo) were inversely associated with RA risk, with Se, Sn, Mn, Sr, and Cr emerging as the main protective factors. A U-shaped relationship emerged between the overall concentrations of these 12 metals and RA risk. TL were inversely associated with RA risk (OR =0.822, 95% CI: 0.689, 0.978). Notably, TL mediated 4.82% of the total effect of Pb exposure on RA risk. Our study reveals that excessive heavy metals and insufficient trace essential elements increase the risk of RA, and emphasizes the potential mediating role of TL in this process.