Global DNA hypomethylation is associated with in utero exposure to cotinine and perfluorinated alkyl compounds.
Environmental exposures in-utero may alter the epigenome, thus impacting chromosomal stability and gene expression. We hypothesized that in utero exposures to maternal smoking and perfluoroalkyl compounds (PFCs) are associated with global DNA hypomethylation in umbilical cord serum. Our objective was to determine if global DNA methylation could be used as a biomarker of in utero exposures to maternal smoking and PFCs. Using an ELISA-based method, global DNA methylation was quantified in umbilical cord serum from 30 newborns with high (> 10 ng/ml, mean 123.8 ng/ml), low (range 1-10 ng/ml, mean 1.6 ng/ml) and very low (< 1 ng/ml, mean 0.06 ng/ml) cord serum cotinine levels. Y chromosome analysis was performed to rule out maternal DNA cross-contamination. Cord serum global DNA methylation showed an inverse dose response to serum cotinine levels (p< 0.001). Global DNA methylation levels in cord blood were the lowest among newborns with smoking mothers (mean=15.04%; 95% CI, 8.4, 21.7) when compared to babies of mothers who were second-hand smokers (21.1%; 95% CI, 16.6, 25.5) and non-smokers (mean=29.2%; 95% CI, 20.1, 38.1). Global DNA methylation was inversely correlated with serum PFOA (r= -0.72, p < 0.01) but not PFOS levels. Serum Y chromosome analyses did not detect maternal DNA cross-contamination. This study supports the use of global DNA methylation status as a biomarker of in utero exposure to cigarette smoke and PFCs.
Otolaryngology Department, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD, USA. rguerre3@jhmi.edu
Rafael
R
Guerrero-Preston
Lynn R
LR
Goldman
Priscilla
P
Brebi-Mieville
Carmen
C
Ili-Gangas
Cynthia
C
Lebron
Frank R
FR
Witter
Ben J
BJ
Apelberg
Marina
M
Hernández-Roystacher
Andrew
A
Jaffe
Rolf U
RU
Halden
David
D
Sidransky
D000293:Adolescent; D000328:Adult; D002210:Caprylates / Q000009:adverse effects / Q000032:analysis / Q000097:blood; D003367:Cotinine / Q000009:adverse effects* / Q000097:blood; D019175:DNA Methylation / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005466:Fluorocarbons / Q000009:adverse effects* / Q000032:analysis / Q000097:blood / Q000737:chemistry; D055106:Genome-Wide Association Study; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D008875:Middle Aged; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D014599:Uterus; D055815:Young Adult
D002210:Caprylates; D005466:Fluorocarbons; D014028:Tobacco Smoke Pollution; C023036:perfluorooctanoic acid; D003367:Cotinine