DNA methylation signatures of arsenic exposure and obesity

Abstract

Emerging evidence suggests a link between environmental pollution and epigenetic alterations, prompting the need for comprehensive investigations into the relationship between pollutants and health conditions in human populations. This study investigates the interplay between obesity and exposure to toxic metals, examining clinical, serum metal concentrations, and epigenetic signatures. Our approach included serum metal concentration analysis by inductively coupled plasma mass spectrometry and epigenetic analysis using 450k Illumina BeadChips data. Singular value decomposition and linear regression models were used to identify metal associations with DNA methylation. Marked differences were evident in weight, body mass index, glycaemia, High Density Lipoprotein cholesterol (HDL-c), and triglycerides between patients with obesity and without obesity. Metal serum concentrations revealed higher arsenic levels in participants with obesity, while elevated mercury concentrations were found in individuals without obesity. Epigenetic analysis identified 2045 arsenic-associated differentially methylated positions (DMPs) in individuals with obesity, including 57 hypermethylated and 159 hypomethylated sites in promoter regions. These DMPs demonstrated direct associations of arsenic exposure, and traits such as insufficient sleep, smoking, and diseases such as gestational diabetes. Functional enrichment analysis (using traits, gene ontology, and KEGG pathways) highlighted pathways linking obesity and arsenic exposure, specifically the Wnt and TNF signalling pathways. Additionally, hypermethylated sites were linked with cancer, rheumatoid arthritis, and gestational diabetes, emphasizing the intricate relationship between these conditions. Notably, ABCF1 and BRCA1 showed significant differences in methylation associated with arsenic and obesity. The findings provide valuable insights into unravelling the connections between obesity and arsenic exposure, contributing to understand the potential molecular mechanisms and pathways in these intersecting fields.