Poly- and perfluoroalkyl substances (PFASs) and lipidomics and inflammatory proteomics in the human EuroMix study

Abstract

BACKGROUND AND AIM: Exposure to PFASs has been associated with high cholesterol levels, lower vaccination response and higher childhood infections, in epidemiological studies. The mechanistic pathways involved are often unknown. Biomarkers of effect can provide insight in the biological implications of PFAS exposure. We explored the association between serum PFAS concentrations, lipoprotein particle subclasses and inflammatory biomarkers. METHODS: In 127 adult participants of the EuroMix human biomonitoring study (mean age: 40 years, 70% women) we determined the concentrations and lipid content of the major lipoproteins in two plasma samples by nuclear magnetic resonance and the serum concentrations of five perfluoroalkyl sulfonates (PFSAs) and six perfluoroalkyl carboxylates (PFCAs), and analysed their association by linear mixed-effect regression models. Further, we used an OLINK high-throughput proteomic assay to analyze plasma inflammatory proteins and explored the association with PFAS by linear regression analysis. RESULTS:Most PFCAs, and PFOS were positively associated with HDL and LDL cholesterol concentrations and negatively associated with VLDL cholesterol and triglyceride concentrations in all lipoproteins. One interquartile range (IQR) increase in PFNA, PFDoDA and PFOS was associated with 11%-12% higher HDL cholesterol, independent of HDL particle size. One IQR increase in PFTrDA, PFHpS and PFOS was associated with 9%-14% higher cholesterol concentrations in the small-size LDL. Long-chain PFCAs were negatively associated with the cholesterol and triglyceride concentrations in the large- and mid-sized VLDL subfractions. We found mostly negative associations between PFAS and inflammatory biomarkers. One IQR increase in PFOS, PFNA, PFDA, PFUnDA and PFDoDA was associated with 2-3% lower anti-inflammatory factors, HGF and IL-10RB. CONCLUSIONS:In this exploratory study, we aimed to identify serum lipoprotein and inflammatory biomarkers as markers of exposure to PFAS. We observed that PFAS exposure may influence the distribution and lipid composition of major lipoprotein subclasses, as well as modulation of inflammatory responses. KEYWORDS: Proteomics, PFAS, Cardiovascular diseases, Toxicology