Serum microRNA biomarker identification in a residential cohort with elevated polychlorinated biphenyl exposures.
Citation:
Chorley, B., C. Pinkston, S. Rai, H. Clair, J. Hardesty, G. Carswell, G. Nelson, M. Pavuk, AND M. Cave. Serum microRNA biomarker identification in a residential cohort with elevated polychlorinated biphenyl exposures. Dioxin 2017, Vancouver, canada, CANADA, August 20 - 25, 2017.
Impact/Purpose:
This study is testing the utility of epigenetic-based biomarkers to identify individuals with liver disease associated with high PCB exposure. These epigenetic biomarkers (microRNA) are being measured in the serum that has been archived for approximately a decade. There is large amount of data available for these samples, therefore, we can correlate with these measurements that include liver toxicity biomarkers, inflammation, metabolic syndrome biomarkers and PCB levels (among others). To our knowledge, these microRNA data are the first ever generated in an environmental hepatology study. This type of data is important to Agency because these mechanism-based biomarkers can be utilized in screening paradigms, as well as used to identify subpopulations that may be susceptible or influenced by environmental chemical hazards (in this case liver disease).
Description:
Toxicant-associated steatohepatitis (TASH) is a form of liver disease associated with both industrial [1] and environmental [2] chemical exposures. Like other forms of Non-alcoholic Fatty Liver Disease (NAFLD), TASH can contribute to systemic metabolic disease states and may progress to cirrhosis and increase risk for cancer. Unlike other forms of NAFLD, however, TASH is unlikely to be detected incidentally or through conventional screening tests such as serum alanine transaminase [ALT] or aspartate transaminase [AST] activity [1]. New liver injury biomarkers that can detect this unique form of steatohepatitis will help identify subpopulations susceptible to advanced liver diseases and associated metabolic conditions. MicroRNAs (miRs) are non-coding regulators of gene transcription and translation that maintain cellular homeostasis and mediate responses to environmental exposures. In recent years, miRs have been found to be stable in accessible matrices such blood, urine, saliva and other biofluids. Some miRs found in these biofluids are sourced from specific tissues and may serve as biomarkers of tissue perturbation and early disease processes, including fatty liver disease and hepatotoxicity [3]. Polychlorinated biphenyls (PCBs) were manufactured from 1929-1971at a facility in Anniston, Alabama, and release of PCB-containing waste resulted in high local levels of environmental contamination. Concerns over the health effects of this contamination prompted the Agency for Toxic Substances Disease Registry (ATSDR) to partner with community members and university researchers to fund an exposure and health effects survey. The result was the Anniston Community Health Survey (ACHS) study cohort. TASH was previously associated with exposures to specific PCB congeners in ACHS [4]. We hypothesized that previously identified individuals with TASH in the ACHS study cohort will exhibit an altered liver miR profile in serum compared to those without TASH.