The association between total serum isomers of per- and polyfluoroalkyl substances, lipid profiles, and the DNA oxidative/nitrative stress biomarkers in middle-aged Taiwanese adults.

Per- and polyfluoroalkyl substances (PFAS) have been widely used in consumer products. In vitro and animal studies have demonstrated that exposure to perfluorooctanoic acid (PFOA) and/or perfluorooctane sulfonate (PFOS) increases oxidative/nitrative stress. Recent studies have also found that isomers of PFOA/PFOS may have unique biological effects on clinical parameters. However, the correlation between PFOA/PFOS isomers and markers of oxidative/nitrative stress has never been investigated in the general population. In the current study, 597 adult subjects (ages between 22 and 63 years old) were enrolled from a control group of a case-control study entitled "Work-related risk factors and coronary heart disease". We investigated the correlation between the serum isomers of PFOA/PFOS, lipid profiles, and the urine compounds 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-nitroguanine (8-NO2Gua) in these participants. There were 519 men and 78 women with a mean age of 45.8 years. Linear PFOA levels were positively correlated with serum low density lipoprotein cholesterol (LDL-C), small dense LDL, and triglyceride, and linear PFOS levels were positively correlated with LDL-C and HDL-C in multiple linear regression analyses. After controlling for potential confounders, the mean levels of 8-OHdG and 8-NO2Gua significantly increased across the quartiles of linear PFOS in multiple linear regression analyses. When both the 8-OHdG and 8-NO2Gua levels were above the 50th percentile, the odds ratio (OR) of higher levels of LDL-C (>75th percentile) with one unit increase in ln linear PFOS level was the highest (OR 3.15 (95% CI = 1.45-6.64), P = 0.003) in logistic regression models. In conclusion, serum linear PFOA/PFOS were correlated with lipid profiles, and linear PFOS was associated with urine oxidative/nitrative stress biomarkers. The positive correlation between linear PFOS and LDL-C was more marked when concentrations of urine oxidative/nitrative stress biomarkers were elevated. Further studies are needed to elucidate the causal relationships among PFAS isomers, lipid profiles, and oxidative/nitrative stress.

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