TitleDifferential DNA methylation in umbilical cord blood of infants exposed to mercury and arsenic in utero.
Publication TypeJournal Article
Year of Publication2015
AuthorsCardenas, A, Koestler, DC, E Houseman, A, Jackson, BP, Kile, ML, Karagas, MR, Marsit, CJ
Date Published2015
KeywordsAdolescent, Adult, Arsenic, B-Lymphocytes, CpG Islands, DNA Methylation, Environmental Exposure, Epigenesis, Genetic, Female, Fetal Blood, Humans, Infant, Newborn, Leukocytes, Male, Mercury, Middle Aged, Pregnancy

Mercury and arsenic are known developmental toxicants. Prenatal exposures are associated with adverse childhood health outcomes that could be in part mediated by epigenetic alterations that may also contribute to altered immune profiles. In this study, we examined the association between prenatal mercury exposure on both DNA methylation and white blood cell composition of cord blood, and evaluated the interaction with prenatal arsenic exposure. A total of 138 mother-infant pairs with postpartum maternal toenail mercury, prenatal urinary arsenic concentrations, and newborn cord blood were assessed using the Illumina Infinium Methylation450 array. White blood cell composition was inferred from DNA methylation measurements. A doubling in toenail mercury concentration was associated with a 2.5% decrease (95% CI: 5.0%, 1.0%) in the estimated monocyte proportion. An increase of 3.5% (95% CI: 1.0, 7.0) in B-cell proportion was observed for females only. Among the top 100 CpGs associated with toenail mercury levels (ranked on P-value), there was a significant enrichment of loci located in North shore regions of CpG islands (P = 0.049), and the majority of these loci were hypermethylated (85%). Among the top 100 CpGs for the interaction between arsenic and mercury, there was a greater than expected proportion of loci located in CpG islands (P = 0.045) and in South shore regions (P = 0.009) and all of these loci were hypermethylated. This work supports the hypothesis that mercury may be contributing to epigenetic variability and immune cell proportion changes, and suggests that in utero exposure to mercury and arsenic, even at low levels, may interact to impact the epigenome.

Alternate JournalEpigenetics
PubMed ID25923418
PubMed Central IDPMC4622995
Grant ListP42 ES007373 / ES / NIEHS NIH HHS / United States
KL2TR000119 / TR / NCATS NIH HHS / United States
K01 ES017800 / ES / NIEHS NIH HHS / United States
P01 ES022832 / ES / NIEHS NIH HHS / United States
R01 ES023441 / ES / NIEHS NIH HHS / United States
P42 ES016465 / ES / NIEHS NIH HHS / United States
KL2 TR000119 / TR / NCATS NIH HHS / United States