Arsenic Exposure and DNA Methylation Among Elderly Men

Abstract

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. 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. 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]). 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.