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Prenatal exposure to phthalates and peripheral blood and buccal epithelial DNA methylation in infants : An epigenome-wide association study

England-Mason, Gillian (författare)
Merrill, Sarah M. (författare)
Gladish, Nicole (författare)
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Moore, Sarah R. (författare)
Giesbrecht, Gerald F. (författare)
Letourneau, Nicole (författare)
MacIsaac, Julia L. (författare)
MacDonald, Amy M. (författare)
Kinniburgh, David W. (författare)
Ponsonby, Anne-Louise (författare)
Saffery, Richard (författare)
Martin, Jonathan W. (författare)
Stockholms universitet,Institutionen för miljövetenskap,Science for Life Laboratory (SciLifeLab)
Kobor, Michael S. (författare)
Dewey, Deborah (författare)
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 (creator_code:org_t)
Elsevier BV, 2022
2022
Engelska.
Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 163
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Background: Prenatal exposure to phthalates has been associated with adverse health and neurodevelopmental outcomes. DNA methylation (DNAm) alterations may be a mechanism underlying these effects, but prior investigations of prenatal exposure to phthalates and neonatal DNAm profiles are limited to placental tissue and umbilical cord blood.Objective: Conduct an epigenome-wide association study (EWAS) of the associations between prenatal exposure to phthalates and DNAm in two accessible infant tissues, venous buffy coat blood and buccal epithelial cells (BECs).Methods: Participants included 152 maternal-infant pairs from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Maternal second trimester urine samples were analyzed for nine phthalate metabolites. Blood (n = 74) or BECs (n = 78) were collected from 3-month-old infants and profiled for DNAm using the Infinium HumanMethylation450 (450K) BeadChip. Robust linear regressions were used to investigate the associations between high (HMWPs) and low molecular weight phthalates (LMWPs) and change in methylation levels at variable Cytosine-phosphate-Guanine (CpG) sites in infant tissues, as well as the sensitivity of associations to potential confounders.Results: One candidate CpG in gene RNF39 reported by a previous study examining prenatal exposure to phthalates and cord blood DNAm was replicated. The EWAS identified 12 high-confidence CpGs in blood and another 12 in BECs associated with HMWPs and/or LMWPs. Prenatal exposure to bisphenol A (BPA) associated with two of the CpGs associated with HMWPs in BECs.Discussion: Prenatal exposure to phthalates was associated with DNAm variation at CpGs annotated to genes associated with endocrine hormone activity (i.e., SLCO4A1, TPO), immune pathways and DNA damage (i.e., RASGEF1B, KAZN, HLA-A, MYO18A, DIP2C, C1or109), and neurodevelopment (i.e., AMPH, NOTCH3, DNAJC5). Future studies that characterize the stability of these associations in larger samples, multiple cohorts, across tissues, and investigate the potential associations between these biomarkers and relevant health and neurodevelopmental outcomes are needed.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Hälsovetenskap -- Arbetsmedicin och miljömedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Health Sciences -- Occupational Health and Environmental Health (hsv//eng)

Nyckelord

Phthalates
Neurodevelopment
Epigenetics
450K
DNA methylation
APrON study

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