Relationship of single and co-exposure of per-and polyfluoroalkyl substances and their alternatives with uric acid: A community-based study in China

Numerous studies have suggested per-and polyfluoroalkyl substances (PFASs) are related to uric acid levels, but evidence related to PFAS alternatives is limited. Moreover, the effect of the combined exposure to PFASs and their alternatives on uric acid has not been reported. Hence, we conducted a cross-sectional study involving 1312 adults in Guangzhou, China. Generalized linear regression model was adopted to explore the effect of single PFAS exposure on serum uric acid levels. Further, multi-pollutant models such as Bayesian kernel machine regression, weighted quantile sum, and quantile G-computation were employed to investigate the combined association of PFASs and alternatives with serum uric acid levels. We performed molecular docking to understand the potential interaction of PFAS with Organic Anion Transporters (OATs), involved in the secretion of uric acid. Per log serum 6:2 Cl-PFESA and PFOA increases were accompanied with an increase of serum uric acid with statistical significance (for 6:2 Cl-PFESA: beta: 0.19 ng/mL, 95% CI 0.11–0.26 and for PFOA: beta: 0.43 ng/mL, 95% CI 0.34–0.52). The associations were strongest among overweight and elderly. Multi-pollutant models also revealed a positive association. These positive associations may be PFASs can competitively combine with OAT1 and OAT3, leading to the increase of serum uric acid.