Isomers of per- and polyfluoroalkyl substances and uric acid in adults: Isomers of C8 Health Project in China.

Greater levels of serum per- and polyfluoroalkyl substances (PFAS) are known to be associated with higher uric acid which itself leads to a number of chronic diseases. However, whether this association varies across PFAS isomers which recently have been found to be associated with human health remains unknown. To address this research gap, we explored isomer-specific associations between serum PFAS and uric acid in Chinese adults. We conducted a cross-sectional study of associations between serum PFAS isomer and serum uric acid in 1612 participants from the Isomer of C8 Health Project. We used multivariable linear and logistic regression models to analyze serum isomers of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and other PFASs as continuous and categorical predictors of uric acid, adjusted for confounders. The association was also stratified by kidney function stage based on estimated glomerular filtration rate (GF-1, GF-2, GF-3a, and GF-3b/4). We found positive associations between serum PFAS isomer concentrations and uric acid. Uric acid levels were greater for each log-unit increase in branched PFOA (β = 0.30, 95% CI: 0.21, 0.40), linear PFOA (β = 0.18, 95% CI: 0.09, 0.26), branched PFOS (β = 0.09, 95% CI: 0.02, 0.17) and linear PFOS (β = 0.06, 95% CI: -0.01, 0.14) concentration. The associations between PFAS and uric acid showed an inverted 'U' shaped pattern across kidney function stages. For example, uric acid level was greater with each log-unit increase in total-PFOA among GF-1 (β = 0.21, 95% CI: 0.06, 0.37), this relationship was greater in GF-3a (β = 0.49, 95% CI: 0.09, 0.89) and decreased in GF-3b/4 (β = -0.22, 95% CI: -0.83, 0.39). We also found the odds of hyperuricemia increased linearly with increasing branched PFOA in quartiles (odds ratio = 2.67, 95% CI: 1.86, 3.85 at the highest quartile). We report novel results in which PFAS associations with uric acid varied according to isomer and adult kidney function. Besides, our findings are consistent with previous epidemiologic studies in finding a positive association between serum PFAS concentrations and serum uric acid, especially for PFOA. Our results indicate that more research is needed to more clearly assess the impact of PFAS isomers on human health, which will help to refine regulation policies for PFAS.

Zeng XW ，Lodge CJ ，Dharmage SC ，Bloom MS ，Yu Y ，Yang M ，Chu C ，Li QQ ，Hu LW ，Liu KK ，Yang BY ，Dong GH ... -  《-》

Isomers of perfluoroalkyl substances and overweight status among Chinese by sex status: Isomers of C8 Health Project in China.

Previous investigations on the associations of polyfluoroalkyl substances (PFASs) with overweight/obesity are mixed. Moreover, little information has been reported about the association between isomers of PFASs with body mass index (BMI), waist circumference (WC) or overweight. To address this shortcoming in the literature, we conducted a study involving 1612 Chinese adults (1204 men and 408 women), ages 22-96 years old, from Shenyang, China, to analyze serum isomers of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and other PFASs. Height, weight and WC were measured by a standardized protocol of WHO. Results indicated that increased serum concentrations of all (both branched and linear) isomers of PFASs were associated with a higher prevalence of overweight, and these associations were more pronounced in women. The adjusted odds ratios (ORs) from logistic regression analyses among women were 1.45 (95% confidence interval [CI]: 1.06, 1.99) for linear PFOS isomers, 1.33 (95% CI: 1.00, 1.77) for branched PFOS isomers, 1.39 (95% CI: 1.06, 1.81) for 3 + 4 + 5m PFOS, 1.54 (95% CI: 1.08, 2.21) for linear PFOA isomers, and 1.62 (95% CI: 1.05, 2.51) for branched PFOA isomers, respectively. Associations with increased WC were yielded a similar pattern. Linear regression models also showed positive associations between PFASs and BMI or WC. In conclusion, this study suggests that PFASs and their isomers are positively associated with overweight or increased WC, and the associations are stronger in women. Furthermore, PFOA and its isomers displayed the most robust obesogenic associations.

Tian YP ，Zeng XW ，Bloom MS ，Lin S ，Wang SQ ，Yim SHL ，Yang M ，Chu C ，Gurram N ，Hu LW ，Liu KK ，Yang BY ，Feng D ，Liu RQ ，Nian M ，Dong GH ... -  《-》

Perfluoroalkyl substances follow inverted U-shaped distributions across various stages of glomerular function: Implications for future research.

Data (N = 6844) from National Health and Nutrition Examination Survey for US adults aged ≥ 20 years for the years 2007-2014 were analyzed to evaluate distributional characteristics of selected perfluoroalkyl substances (PFAS) - perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonate (PFHxS) and perfluorononanoic acid (PFNA) with declining glomerular function. The population was stratified according to the estimated glomerular filtration rates (eGFR) that accompany the stages of kidney disease, designated as glomerular function-1 (GF-1, eGFR>90 mL/min/1.73 m2); GF-2 (eGFR 60-89 mL/min/1.73 m2), GF-3A (eGFR 45-59 mL/min/1.73 m2), and GF-3B and 4 combined (eGFR 15-44 mL/min/1.73 m2). Unadjusted as well as adjusted geometric means for serum PFOA, PFDA, PFHxS, and PFNA increased as expected through stage GF-3A but decreased below the concentrations associated with GF-1 for those who were in GF-3B/4. For example, unadjusted geometric means for PFOA were 2.59, 3.02, 3.01, and 2.22 ng/mL for GF-1, GF-2, GF-3A, and GF-3B/4 respectively. Adjusted geometric means for PFOA were 2.34, 2.83, 2.83, and 1.81 ng/mL for GF-1, GF-2, GF-3A, and GF-3B/4 respectively. Thus, PFAS were found to follow inverted U-shaped distributions across different stages of glomerular function. For females, decreases in adjusted PFAS serum levels were initiated at GF-3A, while decreases for males began as early as GF-2. Usually, females are known to have lower levels of PFAS but when in GF-3A and GF-3B/4, females were found to have higher levels of PFAS than males. Thus, inverted U-shaped curves for males and females intersected between GF-2 and GF-3A for PFOA and PFHxS and at GF-3A for PFOS and PFNA. Associations between PFAS and biomarkers of kidney function may be modified in both magnitude and even in direction as kidney function deteriorates. These findings have implications for studies that evaluate associations between PFAS and disease states that affect kidney function, as well as outcome biomarkers known to be affected by kidney function.

Jain RB ，Ducatman A 《-》

Exposure to isomers of per- and polyfluoroalkyl substances increases the risk of diabetes and impairs glucose-homeostasis in Chinese adults: Isomers of C8 health project.

Per- and polyfluoroalkyl substances (PFAS) exposure has been linked to diabetes, but evidence on the association of isomers of PFAS with type 2 diabetes (T2D) remains scant. This population based cross-sectional study aimed to investigate associations between serum PFAS isomers, glucose-homeostasis markers and T2D, adjusted for multiple potential confounders. We used data from "Isomers of C8 Health Project in China" from July 2015 to October 2016. A total of 10 PFAS including isomers of PFOS and PFOA were measured in serum of 1045 Chinese adults. Fasting blood glucose, fasting insulin, homeostasis model of insulin (HOMA-IR) and beta cell function (HOMA-β) were considered as markers of glucose-homeostasis. We found significant positive associations between serum PFAS isomers and glucose-homeostasis markers, namely, fasting blood glucose, fasting insulin and HOMA-IR. Per log-unit increase in branched (br)-PFOS concentration was associated with increased fasting blood glucose (β = 0.25, 95% CI: 0.18, 0.33), fasting insulin (β = 2.19, 95% CI: 1.44, 2.93) and HOMA-IR (β = 0.69, 95% CI: 0.50, 0.89). As compared to br-PFOS, linear (n)-PFOS and -PFOA showed lesser significant associations with glucose-homeostasis makers. Further, exposure to all PFAS including isomeric PFOS, PFOA and PFHxS increased the risk of T2D with br-PFOS exhibiting the highest risk (OR = 5.41, 95% CI: 3.68-7.96). The associations were stronger among women than men. In conclusion, chronic exposure to PFAS isomers was associated with impaired glucose-homeostasis and may increase the prevalence of T2D in Chinese adults. Given the ubiquity of PFAS in the environment and the public health burden of T2D, future studies are warranted to corroborate the findings.

Zeeshan M ，Zhang YT ，Yu S ，Huang WZ ，Zhou Y ，Vinothkumar R ，Chu C ，Li QQ ，Wu QZ ，Ye WL ，Zhou P ，Dong P ，Zeng XW ，Hu LW ，Yang BY ，Shen X ，Zhou Y ，Dong GH ... -  《-》

Isomers of perfluorooctanesulfonate (PFOS) in cord serum and birth outcomes in China: Guangzhou Birth Cohort Study.

Prior investigations on the associations of polyfluoroalkyl substances (PFASs) with fetal growth are mixed. Moreover, little research has accrued pertaining to the association between isomers of PFASs with gestational age and birth weight. To address this gap and present novel information, we conducted a study including 321 pairs of mothers and their infants recruited from Guangzhou, China. High performance liquid chromatography-mass spectrometry was utilized to analyze isomers of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA) along with other PFAS levels in cord serum samples. Mothers' and infants' characteristics were gathered from medical records. The resulting data revealed that higher PFOS, PFOA and isomers of PFOS were associated with lower birth weight. Per ln-unit (ng/mL) increase in cord serum total branched PFOS isomers was associated with a 126.3g (95% CI: -195.9, -56.8) reduction in the weight of infants at birth, while an ln-unit (ng/mL) increase of serum linear PFOS isomers (n-PFOS) was associated with a 57.2g (95% CI: -103.1, -11.3) reduction in the weight of infants at birth upon the subsequent adjustment for potential confounding variables. Notably, the association between cord PFAS level and birth weight was more pronounced in male infants. Furthermore, a positive association among branched PFOS isomers (1m-PFOS and 3+4+5m-PFOS) and gestational age was found. No associations could be found among other PFASs in conjunction with gestational age or birth weight. In conclusion, this investigation suggests that higher PFAS concentrations are associated with lower birth weight, and branched PFOS isomers show greater impact on infant birth weight than linear PFOS.

Li M ，Zeng XW ，Qian ZM ，Vaughn MG ，Sauvé S ，Paul G ，Lin S ，Lu L ，Hu LW ，Yang BY ，Zhou Y ，Qin XD ，Xu SL ，Bao WW ，Zhang YZ ，Yuan P ，Wang J ，Zhang C ，Tian YP ，Nian M ，Xiao X ，Fu C ，Dong GH ... -  《-》