RT Journal Article
SR Electronic
T1 Epigenetic biomarkers of autoimmune risk and protective antioxidant signaling in methylmercury-exposed adults
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.07.05.498896
DO 10.1101/2022.07.05.498896
A1 Caren Weinhouse
A1 Luiza Perez
A1 Ian Ryde
A1 Jaclyn M. Goodrich
A1 J. Jaime Miranda
A1 Heileen Hsu-Kim
A1 Susan K. Murphy
A1 Joel N. Meyer
A1 William K. Pan
YR 2022
UL http://biorxiv.org/content/early/2022/07/06/2022.07.05.498896.abstract
AB Background Methylmercury (MeHg) is an environmental pollutant of global public health concern. MeHg is associated with immune dysfunction but the underlying mechanisms are unclear. The most common route of MeHg exposure is through consumption of fatty fish that contain beneficial n-3 polyunsaturated fatty acids (PUFA) that may protect against MeHg toxicity.Objectives To better inform individual costs and benefits of fish consumption, we aimed to identify candidate epigenetic biomarkers of biological responses that reflect MeHg toxicity and PUFA protection.Methods We profiled genome-wide DNA methylation using Illumina Infinium MethylationEPIC BeadChip in whole blood from N=32 individuals from Madre de Dios, Peru. Madre de Dios has high artisanal and small-scale gold mining activity, which results in high MeHg exposure to nearby residents. We compared DNA methylation in N=16 individuals with high (>10 µg/g) vs. N=16 individuals with low (<1 µg/g) total hair mercury (a proxy for methylmercury exposure), matched on age and sex.Results We identified hypomethylated (i.e., likely activated) genes and promoters in high vs. low MeHg-exposed participants linked to Th1/Th2 immune imbalance, decreased IL-7 signaling, and increased marginal zone B cells. These three pathways are feasible mechanisms for MeHg-induced autoimmunity. In addition, we identified candidate epigenetic biomarkers of PUFA-mediated protection: hypomethylated enhancer binding sites for retinoid X receptor (RXR) and retinoic acid receptor α (RARα). Last, we observed hypomethylated enhancer and promoter binding sites for glucocorticoid receptor (GR), which is associated with developmental neurotoxicity, and transcription factor 7-like 2 (TCF7L2), which is associated with type 2 diabetes (T2D) risk.Discussion Here, we identify a set of candidate epigenetic biomarkers for assessing individualized risk of autoimmune response and protection against neurotoxicity due to MeHg exposure and fish consumption. In addition, our results may inform surrogate tissue biomarkers of early MeHg exposure-related neurotoxicity and T2D risk.Competing Interest StatementThe authors have declared no competing interest.