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Association of global DNA methylation and global DNA hydroxymethylation with metals and other exposures in human blood DNA samples.

Authors
Tellez-Plaza-M; Tang-W-y; 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
Source
Environ Health Perspect 2014 Sep; 122(9):946-954
NIOSHTIC No.
20044196
Abstract
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.
Keywords
Humans; Men; Women; Workers; Exposure-levels; Metal-compounds; Metallic-compounds; Chemical-properties; Urinalysis; Antibody-response; Age-groups; Body-weight; Weight-factors; Smoking; Metabolism; Biomarkers; Statistical-analysis; Epidemiology
Contact
Maria Tellez-Plaza, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room W7513D, Baltimore, MD 21205
CODEN
EVHPAZ
CAS No.
7440-38-2
Publication Date
20140901
Document Type
Journal Article
Email Address
mtellezp@jhsph.edu
Funding Type
Grant
Fiscal Year
2014
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-T42-OH-008428; M042014
Issue of Publication
9
ISSN
0091-6765
Source Name
Environmental Health Perspectives
State
MD; DC; TX
Performing Organization
Johns Hopkins University
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