Abstract | BACKGROUND: Prenatal smoking exposure has been associated with childhood attention-deficit/hyperactivity disorder ( ADHD). However, the mechanism underlying this relationship remains unclear. We assessed whether DNA methylation differences may mediate the association between prenatal smoking exposure and ADHD symptoms at the age of 6 years. RESULTS: We selected 1150 mother-infant pairs from the Hokkaido Study on the Environment and Children's Health. Mothers were categorized into three groups according to plasma cotinine levels at the third trimester: non-smokers (≤ 0.21 ng/mL), passive smokers (0.21-11.48 ng/mL), and active smokers (≥ 11.49 ng/mL). The children's ADHD symptoms were determined by the ADHD-Rating Scale at the age of 6 years. Maternal active smoking during pregnancy was significantly associated with an increased risk of ADHD symptoms (odds ratio, 1.89; 95% confidence interval, 1.14-3.15) compared to non-smoking after adjusting for covariates. DNA methylation of the growth factor-independent 1 transcriptional repressor (GFI1) region, as determined by bisulfite next-generation sequencing of cord blood samples, mediated 48.4% of the total effect of the association between maternal active smoking during pregnancy and ADHD symptoms. DNA methylation patterns of other genes ( aryl-hydrocarbon receptor repressor [AHRR], cytochrome P450 family 1 subfamily A member 1 [ CYP1A1], estrogen receptor 1 [ESR1], and myosin IG [MYO1G]) regions did not exert a statistically significant mediation effect. CONCLUSIONS: Our findings demonstrated that DNA methylation of GFI1 mediated the association between maternal active smoking during pregnancy and ADHD symptoms at the age of 6 years.
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Authors | Kunio Miyake, Chihiro Miyashita, Atsuko Ikeda-Araki, Ryu Miura, Sachiko Itoh, Keiko Yamazaki, Sumitaka Kobayashi, Hideyuki Masuda, Tadao Ooka, Zentaro Yamagata, Reiko Kishi |
Journal | Clinical epigenetics
(Clin Epigenetics)
Vol. 13
Issue 1
Pg. 74
(04 07 2021)
ISSN: 1868-7083 [Electronic] Germany |
PMID | 33827680
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA-Binding Proteins
- GFI1 protein, human
- Transcription Factors
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Topics |
- Adult
- Asian People
- Attention Deficit Disorder with Hyperactivity
(chemically induced)
- Child
- DNA Methylation
- DNA-Binding Proteins
(genetics)
- Female
- Gene Expression Regulation
- Humans
- Japan
- Male
- Maternal Exposure
(adverse effects)
- Pregnancy
- Prenatal Exposure Delayed Effects
(genetics)
- Smoking
(adverse effects)
- Transcription Factors
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