Epigenetic influence of human long-term environmental exposure to metals

Background: Long-term environmental exposure to metals leads to epigenetic changes and may increase risks to human health. The relationship between the type, timing and level of metal exposure and DNA methylation is not yet clear. The human epidemiologic and the toxicologic animal model studies provide strong evidence of metal exposure related DNA methylation changes, and, consequently alterations in gene expression, in metabolic, genetic and signal transduction pathways and their functions. However, the studies to understand the molecular basis of sequence specific epigenetic responses to metal exposure, as well as methods for the assessment of epigenetic influence of exposure mixtures in a genome-wide level are required to advance the field. Current study aimed to investigate genome wide DNA methylation changes induced by human chronic environmental exposure to metals. Methods: Exposed and unexposed subjects (n = 100) will be selected based on the distance to mine as well as reports on heavy metal levels in the habitation area. In total, 50 subjects, who are living near the mining region and regularly consume vegetables, fruits, dairy with trace elements concentrations exceeding maximum acceptable levels (Syunik village, Artsvanik village, Kapan city, Armenia) will be recruited in metal-exposed group. 50 subjects living in Yerevan city, Armenia, will be recruited in unexposed group since there is no mining activity around the city. Reduced representation bisulfite sequencing (RRBS) will be used for analyzing the genome-wide methylation profiles in DNA extracted from peripheral blood leukocytes. The libraries will be sequenced on NextSeq2000 system (30x coverage).