Biomarkers of lead exposure and DNA methylation within retrotransposons.
BACKGROUND
DNA methylation is an epigenetic mark that regulates gene expression. Changes in DNA methylation within white blood cells may result from cumulative exposure to environmental metals such as lead. Bone lead, a marker of cumulative exposure, may therefore better predict DNA methylation than does blood lead.


OBJECTIVE
In this study we compared associations between lead biomarkers and DNA methylation.


METHODS
We measured global methylation in participants of the Normative Aging Study (all men) who had archived DNA samples. We measured patella and tibia lead levels by K-X-Ray fluorescence and blood lead by atomic absorption spectrophotometry. DNA samples from blood were used to determine global methylation averages within CpG islands of long interspersed nuclear elements-1 (LINE-1) and Alu retrotransposons. A mixed-effects model using repeated measures of Alu or LINE-1 as the dependent variable and blood/bone lead (tibia or patella in separate models) as the primary exposure marker was fit to the data.


RESULTS
Overall mean global methylation (+/- SD) was 26.3 +/- 1.0 as measured by Alu and 76.8 +/- 1.9 as measured by LINE-1. In the mixed-effects model, patella lead levels were inversely associated with LINE-1 (beta = -0.25; p < 0.01) but not Alu (beta = -0.03; p = 0.4). Tibia lead and blood lead did not predict global methylation for either Alu or LINE-1.


CONCLUSIONS
Patella lead levels predicted reduced global DNA methylation within LINE-1 elements. The association between lead exposure and LINE-1 DNA methylation may have implications for the mechanisms of action of lead on health outcomes, and also suggests that changes in DNA methylation may represent a biomarker of past lead exposure.
Wright
Robert O
RO
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02215 , USA.
Schwartz
Joel
J
Wright
Rosalind J
RJ
Bollati
Valentina
V
Tarantini
Letizia
L
Park
Sung Kyun
SK
Hu
Howard
H
Sparrow
David
D
Vokonas
Pantel
P
Baccarelli
Andrea
A
D015415:Biomarkers / Q000032:analysis*; D001842:Bone and Bones / Q000737:chemistry*; D019175:DNA Methylation / Q000187:drug effects* / Q000235:genetics; D004785:Environmental Pollutants / Q000032:analysis*; D006801:Humans; D007854:Lead / Q000032:analysis*; D007962:Leukocytes / Q000737:chemistry*; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D008404:Massachusetts; D015233:Models, Statistical; D018626:Retroelements / Q000235:genetics*; D013052:Spectrometry, X-Ray Emission; D013054:Spectrophotometry, Atomic
D015415:Biomarkers; D004785:Environmental Pollutants; D018626:Retroelements; D007854:Lead