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Cited by 97Effects and risks of endocrine disrupting chemicalsEpigenetics and DNA MethylationAsthma and respiratory diseases

Effects of phthalate exposure on asthma may be mediated through alterations in DNA methylation

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Wang, I-Jen, Karmaus, Wilfried JJ, Chen, Su-Lien, Holloway, John W, Ewart, Susan·2015·Clinical Epigenetics
DOI 10.1186/s13148-015-0060-xPMC PMC4424541
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Abstract

BACKGROUND: Phthalates may increase the asthma risk in children. Mechanisms underlying this association remain to be addressed. This study assesses the effect of phthalate exposures on epigenetic changes and the role of epigenetic changes for asthma. In the first step, urine and blood samples from 256 children of the Childhood Environment and Allergic diseases Study (CEAS) were analyzed. Urine 5OH-MEHP levels were quantified as an indicator of exposure, and asthma information was collected. DNA methylation (DNA-M) was measured by quantitative PCR. In the screening part of step 1, DNA-M of 21 potential human candidate genes suggested by a toxicogenomic data were investigated in 22 blood samples. Then, in the testing part of step 1, positively screened genes were tested in a larger sample of 256 children and then validated by protein measurements. In step 2, we replicated the association between phthalate exposure and gene-specific DNA-M in 54 children in the phthalate contaminated food event. In step 3, the risk of DNA-M for asthma was tested in 256 children from CEAS and corroborated in 270 children from the Isle of Wight (IOW) birth cohort. RESULTS: Differential methylation in three genes (AR, TNFα, and IL-4) was identified through screening. Testing in 256 children showed that methylation of the TNFα gene promoter was lower when children had higher urine 5OH-MEHP values (β = -0.138, P = 0.040). Functional validation revealed that TNFα methylation was inversely correlated with TNFα protein levels (β = -0.18, P = 0.041). In an additional sample of 54 children, we corroborated that methylation of the TNFα gene promoter was lower when urine 5OH-MEHP concentrations were higher. Finally, we found that a lower methylation of 5'CGI region of TNFα was associated with asthma in 256 CEAS children (OR = 2.15, 95% CI = 1.01 to 4.62). We replicated this in 270 children from the IOW birth cohort study. Methylation of the CpG site cg10717214 was negatively associated with asthma, when children had 'AA' or 'AG' genotype of the TNFα single nucleotide rs1800610. CONCLUSIONS: Effects of phthalate exposure on asthma may be mediated through alterations in DNA methylation.

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  • Urinary MEHP concentrations are correlated with asthma in children.

    “Urinary MEHP concentrations are correlated with asthma in children [203].”

    From A Review of Biomonitoring of Phthalate Exposures (2019) · cites this paper as [203]

    The Results section ('Phthalate exposure was positively associated with asthma'; page not provided) reports a significant association between urinary 5OH-MEHP and asthma in 256 children. The Methods section ('Exposure monitoring'; page not provided) identifies 5OH-MEHP as the measured metabolite. The citing sentence says MEHP, which is not the metabolite reported in this association. (LLM, conf=0.89)

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Cited by

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Authors
Wang, I.-J., Karmaus, W. J., Chen, S.-L., Holloway, J. W., & Ewart, S.
Affiliations
  • China Medical University (TW)
  • University of Memphis (US)
  • National Institute for Health and Care Research (GB)
  • Michigan State University (US)
Corresponding author
Wang, I-Jen
ORCID
Venue
Clinical Epigenetics
Publisher
Springer Science and Business Media LLC
Published
2015-03-15
Volume
7
Issue
1
Pages
27-27
ISSN
  • 1868-7075 (ISSN-L)
  • 1868-7083
DOI
10.1186/s13148-015-0060-x
PMC
PMC4424541
OpenAlex
W2134757331
Cited by
97
References
1
Citations by year
2026: 5 · 2025: 11 · 2024: 4 · 2023: 6 · 2022: 13 · 2021: 9 · 2020: 10 · 2019: 7 · 2018: 10 · 2017: 10 · 2016: 10 · 2015: 2
FWCI
6.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Epigenetics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
Funders
  • National Science Council
  • Ministry of Science and Technology, Taiwan (NSC102-2628-B192-001-MY3)
  • National Institutes of Health (NHLBI R01)
  • National Heart, Lung, and Blood Institute (R01HL082925)
  • National Institute of Allergy and Infectious Diseases (AI091905, R01AI061471, R01AI091905)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
Keywords
phthalate exposure, asthma, DNA methylation, epigenetics, children, urinary biomarkers, AR, IL-4, single nucleotide polymorphisms

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