Effect of prenatal bisphenol A exposure on early childhood body mass index through epigenetic influence on the insulin-like growth factor 2 receptor (IGF2R) gene

[Display omitted] •Prenatal exposure to BPA may affect children’s DNA methylation.•One region in IGF2R was differentially methylated by prenatal BPA exposure.•Methylation of the CpG site at IGF2R at age 2 was associated with BMI at ages 2–8.•The effects of DNA methylation on BMI differed by sex. Epi...

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Published in:Environment international 2020-10, Vol.143, p.105929, Article 105929
Main Authors: Choi, Yoon-Jung, Lee, Young Ah, Hong, Yun-Chul, Cho, Jinwoo, Lee, Kyung-Shin, Shin, Choong Ho, Kim, Bung-Nyun, Kim, Johanna Inhyang, Park, Soo Jin, Bisgaard, Hans, Bønnelykke, Klaus, Lim, Youn-Hee
Format: Article
Language:English
Subjects:
Benzhydryl Compounds - toxicity
Bisphenol A
Body Mass Index
Child
Child, Preschool
DNA Methylation
Epigenesis, Genetic
Epigenetics
Female
Humans
Male
Phenols
Pregnancy
Prenatal
Prenatal Exposure Delayed Effects - genetics
Prospective Studies
Receptor, IGF Type 2 - metabolism
Somatomedins
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Summary:[Display omitted] •Prenatal exposure to BPA may affect children’s DNA methylation.•One region in IGF2R was differentially methylated by prenatal BPA exposure.•Methylation of the CpG site at IGF2R at age 2 was associated with BMI at ages 2–8.•The effects of DNA methylation on BMI differed by sex. Epigenetic mechanisms have been suggested to play a role in the link between in utero exposure to bisphenol A (BPA) and pediatric obesity; however, there is little evidence regarding this mechanism in humans. We obtained data on obesity-associated CpG sites from a previous epigenome-wide association study, and then examined whether methylation at those CpG sites was influenced by prenatal BPA exposure. We then evaluated the relationship between CpG methylation status and body mass index (BMI) in a prospective children’s cohort at ages 2, 4, 6, and 8 years. Methylation profiles of 59 children were longitudinally analyzed at ages 2 and 6 years using the Infinium Human Methylation BeadChip. A total of 594 CpG sites known to be BMI or obesity-associated sites were tested for an association with prenatal BPA levels, categorized into low and high exposure groups based on the 80th percentile of maternal BPA levels (2.68 μg/g creatinine), followed by an analysis of the association between DNA methylation and BMI from ages 2–8. There was a significant increase in the methylation levels of cg19196862 (IGF2R) in the high BPA group at age 2 years (p = 0.00030, false discovery rate corrected p 
ISSN:0160-4120
1873-6750
DOI:10.1016/j.envint.2020.105929