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Persistent organic pollutant exposures are associated with liver toxicity and decreased albumin in a highly exposed human cohort
Citation:
Cave, M., C. Pinkston, S. Rai, B. Wahlang, K. Head, G. Carswell, L. Birnbaum, AND B. Chorley. Persistent organic pollutant exposures are associated with liver toxicity and decreased albumin in a highly exposed human cohort. American Association for the Study of Liver Disease (AASLD) The Liver Meeting, Washington, DC, November 04 - 08, 2022. https://doi.org/10.23645/epacomptox.21717740
Impact/Purpose:
Presentation to the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting November 2022. This study is follow-up cohort of PCB exposed indviduals and dmeonstrates the vailidity of using microRNA biomarkers measurable in the blood as indicators of exposure and liver outcomes, such as non-alcoholic fatty liver disease. By developing these molecular biomarkers of biological effect, we can assess the impact of environemental exposure in a human subpopulation.
Description:
Ortho-substituted PCB exposures have been associated with liver necrosis and circulating microRNAs (miRs) in the Anniston Community Health Survey (ACHS) (PMID:29684222, 34989596). Dioxin-like molecules activate the aryl hydrocarbon receptor (AhR) and have been associated with NAFLD. Here, we determine cross-sectional relationships between persistent organic pollutants including dioxins and liver biomarkers in the follow-up ACHS-II cohort. Methods: Serum biomarkers of pollutant exposure [PCDDs (N=7), PCDFs (N=10), PCBs (N=40), and PBDEs (N=11)] and liver disease [routine chemistries (n=9); keratin-18 (K18, n=2); and hepatoxicity miRs (n=68)] were measured in 339 adult ACHS-II participants. The primary exposure biomarker was total dioxin toxic equivalency (TEQ). Associations were determined by log-transformed linear adjusted models using SAS v9.4 and R. Results: There was a 45.7% prevalence of K18-catogorized necrotic liver disease associated with increased AST, ALT, ALP, and miR-122-5p. Using complete linkage analysis, the liver tests clustered into four groups (G) which were variably linked to steatosis (G2), injury (G1-G4), hepatitis (G4), cirrhosis (G4), and hepatocellular carcinoma (G1-G3). Total dioxin TEQ was inversely associated with G1 (miR-29a-3p, p=0.0004) and G2 [albumin (p=0.03), total protein (p=0.03), and miR-192-5p (p=0.05)] liver biomarkers. Albumin was also inversely associated with PCDD, PCDF, and NO-PCB TEQ sub-groupings and greater than half of abundant (>40% detection rate) dioxin-like congeners including 2,3,7,8-TCDD (p=0.001) and 2,3,4,7,8-PCDF (p=0.01). However, only one abundant non-dioxin-like molecule (PCB 99) was associated with albumin. ∑Non-dioxin like PCBs was inversely associated with miR-29a-3p. All five abundant PBDEs were inversely associated with miR-92a-3p. Three of these PBDEs were positively associated with miR-122-5p and two with K18 M65. Conclusions: The high liver disease prevalence in ACHS was confirmed. Ingenuity Pathway Analysis (Qiagen) yielded insight into the mechanistic roles of circulating miR biomarkers which clustered into four groups. Persistent organic pollutant exposures were associated with circulating miRs and other hepatotoxicity biomarkers. AhR activation by dioxin-like molecules was consistently associated with decreased albumin, and this was a class-specific effect. The regulation of albumin by dioxins warrants additional investigation. This abstract does not necessarily reflect EPA or NIH policy.
URLs/Downloads:
DOI: Persistent organic pollutant exposures are associated with liver toxicity and decreased albumin in a highly exposed human cohort
CAVE_CHORLEY_AASLD 2022 V2 TO STICSREVIEW.PDF (PDF, NA pp, 606.28 KB, about PDF)