Research Advance Publication
Association of Global DNA Methylation and Global DNA Hydroxymethylation with Metals and other Exposures in Human Blood DNA Samples
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Citation: Tellez-Plaza M, Tang WY, Shang Y, Umans JG, Francesconi KA, Goessler W, Ledesma M, Leon M, Laclaustra M, Pollak J, Guallar E, Cole SA, Fallin MD, Navas-Acien A. Association of Global DNA Methylation and Global DNA Hydroxymethylation with Metals and other Exposures in Human Blood DNA Samples. Environ Health Perspect; http://dx.doi.org/10.1289/ehp.1306674.
Received: 19 February 2013
Accepted: 22 April 2014
Advance Publication: 25 April 2014
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Introduction: The association between human blood DNA global methylation and global hydroxymethylation has not been evaluated in population-based studies. No studies have evaluated environmental determinants of global DNA hydroxymethylation, including exposure to metals.
Objective: We evaluated the association between global DNA methylation and global DNA hydroxymethylation in 48 Strong Heart Study participants who had selected metals measured in urine at baseline and DNA available in 1989-1991 and 1998-1999.
Methods: % 5-methylcytosine (5-mC) and % 5-hydroxymethyl-cytosine (5-hmC) levels were measured by capture and detection antibodies followed by colorimetric quantification. We explored the association of participant characteristics (i.e. age, adiposity, smoking, and metal exposure) with both global DNA methylation and global DNA hydroxymethylation.
Results: The Spearman’s correlation coefficient for 5-mC and 5-hmC levels was 0.32 (p –value = 0.03) at visit 1 and 0.54 (p – value < 0.001) at visit 3. Trends for both epigenetic modifications were consistent across potential determinants. In cross-sectional analyses the odds ratios of methylated and hydroxymethylated DNA were 1.56 (95% CI: 0.95, 2.57) and 1.76 (95% CI: 1.07, 2.88), respectively, comparing participants above and below the median of % dimethylarsinate. The corresponding odds ratios were 1.64 (95% CI: 1.02, 2.65) and 1.16 (95% CI: 0.70, 1.94), respectively, comparing participants above and below median cadmium. Arsenic exposure and metabolism were consistently associated with both epigenetic markers in cross-sectional and prospective analyses. The positive correlation of 5-mC and 5-hmC levels was confirmed in an independent study population.
Conclusions: Our findings support that both epigenetic measures are related at the population level. The consistent trends in the associations between these two epigenetic modifications and the characteristics evaluated, specially arsenic exposure and metabolism, suggest the need for understanding which of the two measures is a better biomarker for environmental epigenetic effects in future large-scale epidemiologic studies.
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