Background: 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 for which selected metals had been measured in urine at baseline and DNA was available from 1989–1991 (visit 1) and 1998–1999 (visit 3).
Methods: We measured the percentage of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in samples using 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 = 0.03) at visit 1 and 0.54 (p < 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, for the comparison of participants above and below the median percentage 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, for the comparison of participants above and below the median cadmium level. 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, especially 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.
1Department of Epidemiology, 2Welch Center for Prevention, Epidemiology and Clinical Research, and 3Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; 4Fundacion de Investigacion del Hospital Clinico de Valencia-INCLIVA, Valencia, Spain; 5Department of Respiratory Disease, Changhai Hospital, Second Military Medical University, Shanghai, China; 6MedStar Health Research Institute, Hyattsville, Maryland, USA; 7Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC, USA; 8Institute of Chemistry–Analytical Chemistry, Karl-Franzens University, Graz, Austria; 9Aragon Health Sciences Institute, Zaragoza, Spain; 10Department of Epidemiology, Atherothrombosis and Imaging, National Center of Cardiovascular Research-CNIC, Madrid, Spain; 11Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA; 12Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, USA
Recommended Citation:
Maria Tellez-Plaza,1,2,et al. Association of Global DNA Methylation and Global DNA Hydroxymethylation with Metals and Other Exposures in Human Blood DNA Samples[J]. Environmental Health Perspectives,2014-01-01,Volume 122(Issue 9):946