Arsenic Exposure and DNA Methylation Among Elderly Men

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 B-12), and pyridoxine (vitamin B-6). 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 (beta = 0.08 [95% confidence interval = 0.03 to 0.13] for one interquartile range [0.06 mu g/g] increase in arsenic), whereas a negative association was observed in subjects with plasma folate above the median (beta = -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.