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Fetal lung and placental methylation is associated with in utero nicotine exposure
Open accessAbstract
In utero smoke exposure has been shown to have detrimental effects on lung function and to be associated with persistent wheezing and asthma in children. One potential mechanism of IUS effects could be alterations in DNA methylation, which may have life-long implications. The goal of this study was to examine the association between DNA methylation and nicotine exposure in fetal lung and placental tissue in early development; nicotine exposure in this analysis represents a likely surrogate for in-utero smoke. We performed an epigenome-wide analysis of DNA methylation in fetal lung tissue (n = 85, 41 smoke exposed (48%), 44 controls) and the corresponding placental tissue samples (n = 80, 39 smoke exposed (49%), 41 controls) using the Illumina HumanMethylation450 BeadChip array. Differential methylation analyses were conducted to evaluate the variation associated with nicotine exposure. The most significant CpG sites in the fetal lung analysis mapped to the PKP3 (P = 2.94 × 10(-03)), ANKRD33B (P = 3.12 × 10(-03)), CNTD2 (P = 4.9 × 10(-03)) and DPP10 (P = 5.43 × 10(-03)) genes. In the placental methylome, the most significant CpG sites mapped to the GTF2H2C and GTF2H2D genes (P = 2.87 × 10(-06) - 3.48 × 10(-05)). One hundred and one unique CpG sites with P-values < 0.05 were concordant between lung and placental tissue analyses. Gene Set Enrichment Analysis demonstrated enrichment of specific disorders, such as asthma and immune disorders. Our findings demonstrate an association between in utero nicotine exposure and variable DNA methylation in fetal lung and placental tissues, suggesting a role for DNA methylation variation in the fetal origins of chronic diseases.
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“In addition, adverse health effects caused by SHS may be augmented in children with a genetic susceptibility to asthma, and exposure to tobacco smoke during in utero life may cause epigenetic changes in fetal lung.22”
From Impact of Tobacco Smoke and Nicotine Exposure on Lung Development (2016) · cites this paper as [22]
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“In addition, adverse health effects caused by SHS may be augmented in children with a genetic susceptibility to asthma, and exposure to tobacco smoke during in utero life may cause epigenetic changes in fetal lung.22”
From Impact of Tobacco Smoke and Nicotine Exposure on Lung Development (2016) · cites this paper as [22]
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“One of the first articles looking at the effects of in utero smoke exposure on fetal lung-specific methylation found changes in methylation of DPP10, a gene associated with asthma.22”
From Impact of Tobacco Smoke and Nicotine Exposure on Lung Development (2016) · cites this paper as [22]
In the citing paper
“smoking during pregnancy causes long-lasting changes in DNA methylation if offspring(213) that are observed in fetal lung,(214) cord blood,(214) and which continue to be present in the blood of school-age children.(215)”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [214]
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DNA methylation in newborns and maternal smoking in pregnancy: genome-wide consortium meta-analysis
Joubert, B. R., Felix, J. F., Yousefi, P., Bakulski, K. M., Just, A. C., Breton, C., Reese, S. E., Markunas, C. A., Richmond, R. C., Xu, C.-J., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.02.019 · Cited by 886
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Impact of Tobacco Smoke and Nicotine Exposure on Lung Development
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Metadata
- Authors
- Chhabra, D., Sharma, S., Kho, A. T., Gaedigk, R., Vyhlidal, C. A., Leeder, J. S., Morrow, J., Carey, V. J., Weiss, S. T., Tantisira, K. G., & DeMeo, D. L.
- Affiliations
- Brigham and Women's Hospital (US)
- Children's Mercy Hospital (US)
- Corresponding author
- DeMeo, Dawn L
- ORCID
- Venue
- Epigenetics
- Publisher
- Informa UK Limited
- Published
- 2014-11-02
- Volume
- 9
- Issue
- 11
- Pages
- 1473-1484
- ISSN
- 1559-2294 (ISSN-L)
- 1559-2308
- PMC
- PMC4623268
- OpenAlex
- W2051268137
- Cited by
- 102
- References
- 71
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 10 · 2023: 7 · 2022: 6 · 2021: 10 · 2020: 12 · 2019: 11 · 2018: 13 · 2017: 10 · 2016: 10 · 2015: 6
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Epigenetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5R24 HD0008836, HL007427, HL083069)
- National Heart, Lung, and Blood Institute (K25HL091124, R21HL107927, R01HL089438, R01HL097144, P01HL083069, K08HL096833, T32HL007427)
- U.S. National Library of Medicine (T15LM011271)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- maternal smoking, fetal lung, placenta, DNA methylation, epigenome-wide association study, PKP3, DPP10, asthma, immune disorders
- MeSH terms
- Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Female, Humans, Lung, Male, Nicotine, Placenta, Pregnancy, Case-Control Studies, Maternal Exposure, CpG Islands, DNA Methylation, Genome-Wide Association Study
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