title: Effects of age, sex, and persistent organic pollutants on DNA methylation in children.
abstract: Epigenetic changes such as DNA methylation may be a molecular mechanism through which environmental exposures affect health. Methylation of Alu and long interspersed nucleotide elements (LINE-1) is a well-established measure of DNA methylation often used in epidemiologic studies. Yet, few studies have examined the effects of host factors on LINE-1 and Alu methylation in children. We characterized the relationship of age, sex, and prenatal exposure to persistent organic pollutants (POPs), dichlorodiphenyl trichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and polybrominated diphenyl ethers (PBDEs), with DNA methylation in a birth cohort of Mexican-American children participating in the CHAMACOS study. We measured Alu and LINE-1 methylation by pyrosequencing bisulfite-treated DNA isolated from whole blood samples collected from newborns and nine-year old children (n = 358). POPs were measured in maternal serum during late pregnancy. Levels of DNA methylation were lower in nine-year olds compared to newborns and were higher in boys compared to girls. Higher prenatal DDT/E exposure was associated with lower Alu methylation at birth, particularly after adjusting for cell type composition (P = 0.02 for o,p' -DDT). Associations of POPs with LINE-1 methylation were only identified after examining the co-exposure of DDT/E with PBDEs simultaneously. Our data suggest that repeat element methylation can be an informative marker of epigenetic differences by age and sex and that prenatal exposure to POPs may be linked to hypomethylation in fetal blood. Accounting for co-exposure to different types of chemicals and adjusting for blood cell types may increase sensitivity of epigenetic analyses for epidemiological studies.
authors.affiliation: Center for Children's Environmental Health, School of Public Health, University of California, Berkeley, California.
authors.forename: Karen
authors.initials: K
authors.lastname: Huen
authors.forename: Paul
authors.initials: P
authors.lastname: Yousefi
authors.forename: Asa
authors.initials: A
authors.lastname: Bradman
authors.forename: Liying
authors.initials: L
authors.lastname: Yan
authors.forename: Kim G
authors.initials: KG
authors.lastname: Harley
authors.forename: Katherine
authors.initials: K
authors.lastname: Kogut
authors.forename: Brenda
authors.initials: B
authors.lastname: Eskenazi
authors.forename: Nina
authors.initials: N
authors.lastname: Holland
mesh_terms: D000367:Age Factors; D020087:Alu Elements; D002452:Cell Count; D002648:Child; D015331:Cohort Studies; D003634:DDT / Q000633:toxicity; D019175:DNA Methylation; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity*; D044127:Epigenesis, Genetic; D005260:Female; D005312:Fetal Blood; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity; D006801:Humans; D007231:Infant, Newborn; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D018811:Maternal Exposure; D017058:Mexican Americans; D009930:Organic Chemicals / Q000633:toxicity*; D011247:Pregnancy; D012737:Sex Factors
chemical_list: D004785:Environmental Pollutants; D055768:Halogenated Diphenyl Ethers; D009930:Organic Chemicals; D003633:Dichlorodiphenyl Dichloroethylene; C086401:pentabromodiphenyl ether; D003634:DDT
keywords: Alu; DDE; DDT; LINE-1; PBDE; co-exposure; epigenetics