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An epigenome-wide study of cord blood DNA methylations in relation to prenatal perfluoroalkyl substance exposure : The Hokkaido study

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Title: An epigenome-wide study of cord blood DNA methylations in relation to prenatal perfluoroalkyl substance exposure : The Hokkaido study
Authors: Miura, Ryu Browse this author
Araki, Atsuko Browse this author →KAKEN DB
Miyashita, Chihiro Browse this author →KAKEN DB
Kobayashi, Sumitaka Browse this author →KAKEN DB
Kobayashi, Sachiko Browse this author
Wang, Shu-Li Browse this author
Chen, Chung-Hsing Browse this author
Miyake, Kunio Browse this author
Ishizuka, Mayumi Browse this author →KAKEN DB
Iwasaki, Yusuke Browse this author →KAKEN DB
Ito, Yoichi M. Browse this author →KAKEN DB
Kubota, Takeo Browse this author
Kishi, Reiko Browse this author →KAKEN DB
Keywords: DNA methylation
Perfluoroalkyl substances
Prenatal exposure
Genome-wide association
Cord blood
Issue Date: Jun-2018
Publisher: Elsevier
Journal Title: Environment international
Volume: 115
Start Page: 21
End Page: 28
Publisher DOI: 10.1016/j.envint.2018.03.004
Abstract: Background: Prenatal exposure to perfluoroalkyl substances (PFASs) influences fetal development and later in life. Objective: To investigate cord blood DNA methylation changes associated with prenatal exposure to PFASs. Methods: We assessed DNA methylation in cord blood samples from 190 mother-child pairs from the Sapporo cohort of the Hokkaido Study (discovery cohort) and from 37 mother-child pairs from the Taiwan Maternal and Infant Cohort Study (replication cohort) using the Illumina HumanMethylation 450 BeadChip. We examined the associations between methylation and PFAS levels in maternal serum using robust linear regression models and identified differentially methylated positions (DMPs) and regions (DMRs). Results: We found four DMPs with a false discovery rate below 0.05 in the discovery cohort. Among the top 20 DMPs ranked by the lowest P-values for perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) exposure, four DMPs showed the same direction of effect and P-value < 0.05 in the replication assay: cg16242615 mapped to ZBTB7A, cg21876869 located in the intergenic region (IGR) of USP2-AS1, cg00173435 mapped to TCP11L2, and cg18901140 located in IGR of NTN1. For DMRs, we found a region associated with PFOA exposure with family-wise error rate < 0.1 located in ZFP57, showing the same direction of effect in the replication cohort. Among the top five DMRs ranked by the lowest P-values that were associated with exposure to PFOS and PFOA, in addition to ZFP57, DMRs in the CYP2E1, SMAD3, SLC17A9, GFPT2, DUSP22, and TCERG1L genes showed the same direction of effect in the replication cohort. Conclusion: We suggest that prenatal exposure to PFASs may affect DNA methylation status at birth. Longitudinal studies are needed to examine whether methylation changes observed are associated with differential health outcomes.
Rights: © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:環境健康科学研究教育センター (Center for Environmental and Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 岸 玲子

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