Self-reported prenatal tobacco smoke exposure, AXL gene-body methylation, and childhood asthma phenotypes
Background Epigenetic modifications, including DNA methylation, act as one potential mechanism underlying the detrimental effects associated with prenatal tobacco smoke (PTS) exposure. Methylation in a gene called AXL was previously reported to differ in response to PTS. Methods We investigated the...
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Published in | Clinical epigenetics Vol. 10; no. 1; pp. 98 - 11 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
BioMed Central
20.07.2018
BioMed Central Ltd BMC |
Subjects | |
Online Access | Get full text |
ISSN | 1868-7075 1868-7083 1868-7083 1868-7075 |
DOI | 10.1186/s13148-018-0532-x |
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Summary: | Background
Epigenetic modifications, including DNA methylation, act as one potential mechanism underlying the detrimental effects associated with prenatal tobacco smoke (PTS) exposure. Methylation in a gene called
AXL
was previously reported to differ in response to PTS.
Methods
We investigated the association between PTS and epigenetic changes in
AXL
and how this was related to childhood asthma phenotypes. We tested the association between PTS and DNA methylation at multiple CpG loci of
AXL
at birth using Pyrosequencing in two separate study populations, the Children’s Health Study (CHS, n = 799) and the Newborn Epigenetic Study (NEST, n = 592). Plasma cotinine concentration was used to validate findings with self-reported smoking status. The inter-relationships among
AXL
mRNA and miR-199a1 expression, PTS, and
AXL
methylation were examined. Lastly, we evaluated the joint effects of
AXL
methylation and PTS on the risk of asthma and related symptoms at age 10 years old.
Results
PTS was associated with higher methylation level in the
AXL
gene body in both CHS and NEST subjects. In the pooled analysis, exposed subjects had a 0.51% higher methylation level in this region compared to unexposed subjects (95% CI 0.29, 0.74;
p
< 0.0001). PTS was also associated with 21.2% lower expression of miR-199a1 (95% CI − 37.9, − 0.1;
p
= 0.05), a microRNA known to regulate
AXL
expression. Furthermore, the combination of higher
AXL
methylation and PTS exposure at birth increased the risk of recent episodes of bronchitic symptoms in childhood.
Conclusions
PTS was associated with methylation level of
AXL
and the combination altered the risk of childhood bronchitic symptoms. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
ISSN: | 1868-7075 1868-7083 1868-7083 1868-7075 |
DOI: | 10.1186/s13148-018-0532-x |