The effect of chlorinated solvents on human DNA methylation variability

Introduction: Rosciano and Torre de' Passeri (PE) are two districts located in an area of 300Km2 crossed by the Giardino aqueduct and nearby Bussi Sul Tirino (PE). The resident population in this area was exposed to contamination by chlorinated solvents from 1992 to 2007, due to the incorrect disposal of industrial by-products in the underground and subsequent contamination of the groundwater at the Colle Sant’Angelo well field located 2 km downgradient of the primary source of contamination. Aim: The aim of this project is to describe human-environment interactions and in particular to investigate the effect of chlorinated solvents on human epigenetic variability in term of DNA methylation (DNAm) levels. Methods: DNAm levels were measured through the Bead Chip Infinium Human MethylationEPIC (~ 850,000 CpG sites), considering DNA from buccal swabs. An epigenome-wide analysis to identify differently methylated CpG sites between exposed and not exposed individuals was performed. Subsequently, an F-test was applied to identify CpG sites with significantly different variance between exposed and not exposed individuals. In both analyses, sampling site, exposure to the environmental factor, birth place, residence district, workplace and geographical score were considered. Results: The single CpG sites analyses showed DNAm differences among the above-mentioned groups, while we did not observe statistically significant DMRs (Differentially Methylated Regions). The analyses of variance showed that the variability of individual CpG sites is lower for exposed individuals than for not exposed. Conclusion: From the results obtained, it emerged that the variability of the individual CpG sites appears to be lower for exposed individuals than for not exposed individuals, suggesting an adaptive reduction in epigenetic variability in response to the contaminated environment. Further analysis will be needed to validate these findings.