title: Arsenic and the epigenome: interindividual differences in arsenic metabolism related to distinct patterns of DNA methylation.
abstract: Biotransformation of inorganic arsenic (iAs) is one of the factors that determines the character and magnitude of the diverse detrimental health effects associated with chronic iAs exposure, but it is unknown how iAs biotransformation may impact the epigenome. Here, we integrated analyses of genome-wide, gene-specific promoter DNA methylation levels of peripheral blood leukocytes with urinary arsenical concentrations of subjects from a region of Mexico with high levels of iAs in drinking water. These analyses revealed dramatic differences in DNA methylation profiles associated with concentrations of specific urinary metabolites of arsenic (As). The majority of individuals in this study had positive indicators of As-related disease, namely pre-diabetes mellitus or diabetes mellitus (DM). Methylation patterns of genes with known associations with DM were associated with urinary concentrations of specific iAs metabolites. Future studies will determine whether these DNA methylation profiles provide mechanistic insight into the development of iAs-associated disease, predict disease risk, and/or serve as biomarkers of iAs exposure in humans.
authors: Department of Environmental Sciences and Engineering, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors: Kathryn A
authors: KA
authors: Bailey
authors: Michael C
authors: MC
authors: Wu
authors: William O
authors: WO
authors: Ward
authors: Lisa
authors: L
authors: Smeester
authors: Julia E
authors: JE
authors: Rager
authors: Gonzalo
authors: G
authors: García-Vargas
authors: Luz-Maria
authors: LM
authors: Del Razo
authors: Zuzana
authors: Z
authors: Drobná
authors: Miroslav
authors: M
authors: Stýblo
authors: Rebecca C
authors: RC
authors: Fry
mesh_terms: D001151:Arsenic / Q000493:pharmacokinetics / Q000633:toxicity*; D020261:Arsenic Poisoning / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D044127:Epigenesis, Genetic / Q000187:drug effects*; D057890:Epigenomics / Q000379:methods; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male
chemical_list: D015415:Biomarkers; D001151:Arsenic