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

Gillian England-Mason; Sarah M. Merrill; Nicole Gladish; Sarah R. Moore; Gerald F. Giesbrecht; Nicole Letourneau; Julia L. MacIsaac; Amy M. MacDonald; David W. Kinniburgh; Anne-Louise Ponsonby; Richard Saffery; Jonathan W. Martin; Michael S. Kobor; Deborah Dewey

Environment International (May 2022)

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

Gillian England-Mason,
Sarah M. Merrill,
Nicole Gladish,
Sarah R. Moore,
Gerald F. Giesbrecht,
Nicole Letourneau,
Julia L. MacIsaac,
Amy M. MacDonald,
David W. Kinniburgh,
Anne-Louise Ponsonby,
Richard Saffery,
Jonathan W. Martin,
Michael S. Kobor,
Deborah Dewey

Affiliations

Gillian England-Mason: Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Owerko Centre, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
Sarah M. Merrill: Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children’s Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada
Nicole Gladish: Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children’s Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada
Sarah R. Moore: Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children’s Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada
Gerald F. Giesbrecht: Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Owerko Centre, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada; Department of Psychology, Faculty of Arts, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Nicole Letourneau: Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Owerko Centre, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Faculty of Nursing, University of Calgary, Calgary, Alberta, Canada; Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, Calgary, Alberta, Canada
Julia L. MacIsaac: Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children’s Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada
Amy M. MacDonald: Alberta Centre for Toxicology, University of Calgary, Calgary, Alberta, Canada
David W. Kinniburgh: Alberta Centre for Toxicology, University of Calgary, Calgary, Alberta, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada
Anne-Louise Ponsonby: Murdoch Children’s Research Institute, Royal Children’s Hospital, University of Melbourne, Melbourne, Victoria, Australia
Richard Saffery: Murdoch Children’s Research Institute, Royal Children’s Hospital, University of Melbourne, Melbourne, Victoria, Australia
Jonathan W. Martin: Science for Life Laboratory, Department of Environmental Science, Stockholm University, Stockholm, Södermanland, Sweden
Michael S. Kobor: Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children’s Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada; Program in Child and Brain Development, CIFAR, Toronto, Ontario, Canada
Deborah Dewey: Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Owerko Centre, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, Calgary, Alberta, Canada; Corresponding author at: Department of Paediatrics, University of Calgary, #397 Owerko Center, Child Development Centre, 2500 University Dr. NW, Calgary, Alberta T2N 1N4, Canada.

Journal volume & issue: Vol. 163
p. 107183

Abstract

Read online

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.

Published in Environment International

ISSN: 0160-4120 (Print)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/environment-international

About the journal

Abstract

Keywords