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Arsenic Exposure and DNA Methylation Among Elderly Men

Lambrou, Angelikia,b; Baccarelli, Andreaa; Wright, Robert O.a,c; Weisskopf, Marca,b; Bollati, Valentinad; Amarasiriwardena, Chitrac; Vokonas, Pantele,f; Schwartz, Joela,b

doi: 10.1097/EDE.0b013e31825afb0b
DNA Methylation

Background: Arsenic exposure has been linked to epigenetic modifications such as DNA methylation in in-vitro and animal studies. This association has also been explored in highly exposed human populations, but studies among populations environmentally exposed to low arsenic levels are lacking.

Methods: We evaluated the association between exposure to arsenic, measured in toenails, and blood DNA methylation in Alu and Long Interspersed Nucleotide Element-1 (LINE-1) repetitive elements in elderly men environmentally exposed to low levels of arsenic. We also explored potential effect modification by plasma folate, cobalamin (vitamin B12), and pyridoxine (vitamin B6). The study population was 581 participants from the Normative Aging Study in Boston, of whom 434, 140, and 7 had 1, 2, and 3 visits, respectively, between 1999–2002 and 2006–2007. We used mixed-effects models and included interaction terms to assess potential effect modification by nutritional factors.

Results: There was a trend of increasing Alu and decreasing LINE-1 DNA methylation as arsenic exposure increased. In subjects with plasma folate below the median (<14.1 ng/mL), arsenic was positively associated with Alu DNA methylation (β = 0.08 [95% confidence interval = 0.03 to 0.13] for one interquartile range [0.06 μg/g] increase in arsenic), whereas a negative association was observed in subjects with plasma folate above the median (β = −0.08 [−0.17 to 0.01]).

Conclusions: We found an association between arsenic exposure and DNA methylation in Alu repetitive elements that varied by folate level. This suggests a potential role for nutritional factors in arsenic toxicity.

Supplemental Digital Content is available in the text.

From the aExposure, Epidemiology and Risk Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA; bDepartment of Epidemiology, Harvard School of Public Health, Boston, MA; cChanning Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; dCenter of Molecular and Genetic Epidemiology, Universitá degli Studi di Milano & IRCCS Ca', Granda Policlinico Maggiore Hospital Foundation, Milan, Italy; eVA Normative Aging Study, Veterans Affairs Boston Healthcare System, Boston, MA; and fDepartment of Medicine, Boston University School of Medicine, Boston, MA.

Submitted 10 May 2011; accepted 28 February 2012.

Supported by the National Institute of Environmental Health Sciences (NIEHS) grants ES015172-04, ES014663-03 and ES000002-47. The VA Normative Study, a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts, is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article ( This content is not peer-reviewed or copy-edited; it is the sole responsibility of the author.

Correspondence: Angeliki Lambrou, Exposure, Epidemiology and Risk Program, Department of Environmental Health, Harvard School of Public Health, 401 Park Drive, Landmark Center, Suite 415 West, Boston, MA 02215. E-mail:

© 2012 Lippincott Williams & Wilkins, Inc.