Get access

Arsenic and the Epigenome: Interindividual Differences in Arsenic Metabolism Related to Distinct Patterns of DNA Methylation

Authors

  • Kathryn A. Bailey,

    1. Department of Environmental Sciences and Engineering, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Search for more papers by this author
  • Michael C. Wu,

    1. Department of Biostatistics, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Search for more papers by this author
  • William O. Ward,

    1. National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA
    Search for more papers by this author
  • Lisa Smeester,

    1. Department of Environmental Sciences and Engineering, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Search for more papers by this author
  • Julia E. Rager,

    1. Department of Environmental Sciences and Engineering, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Search for more papers by this author
  • Gonzalo García-Vargas,

    1. Faculty of Medicine, Juarez University of Durango State, Durango, Mexico
    Search for more papers by this author
  • Luz-Maria Del Razo,

    1. Department of Toxicology, CINVESTAV-IPN, Mexico City, Mexico
    Search for more papers by this author
  • Zuzana Drobná,

    1. Department of Nutrition, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Search for more papers by this author
  • Miroslav Stýblo,

    1. Department of Environmental Sciences and Engineering, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    2. Department of Nutrition, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Search for more papers by this author
  • Rebecca C. Fry

    Corresponding author
    • Department of Environmental Sciences and Engineering, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Search for more papers by this author

  • Contract Grant Sponsor: National Institute of Environmental Health Sciences.

  • Contract Grant Numbers: P30ES010126, ES019315, ES015326, DK056350, and T32 ES007018.

Correspondence to: Rebecca C. Fry.

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. © 2012 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:106-115, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21462

Get access to the full text of this article

Ancillary