Prenatal smoke exposure, DNA methylation, and childhood atopic dermatitis
Article first published online: 22 APR 2013
© 2013 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 43, Issue 5, pages 535–543, May 2013
How to Cite
Clinical & Experimental Allergy 2013 (43)535–543., , , , .
- Issue published online: 22 APR 2013
- Article first published online: 22 APR 2013
- Accepted manuscript online: 4 MAR 2013 11:46AM EST
- Manuscript Accepted: 4 FEB 2013
- Manuscript Revised: 1 FEB 2013
- Manuscript Received: 17 MAY 2012
- National Science Council. Grant Number: NSC 98-2314-B-192-001-MY3
- Department of Health in Taiwan
- atopic dermatitis;
- DNA methylation;
- prenatal smoke
The biological mechanisms of how prenatal smoke exposure leading to atopic disorders remain to be addressed. Whether prenatal smoke exposure affects DNA methylation leading to atopic disorders is not clear.
As most children suffering from atopic dermatitis (AD) continue to develop asthma later in life, we explored whether prenatal smoke exposure induces cord blood DNA methylation.
Methylation differences associated with smoke exposure were screened by Illumina Infinium 27K methylation arrays for 14 children from the Taiwan birth panel study cohort initially. Information about development of atopic dermatitis (AD) and risk factors was collected. Cord blood cotinine levels were measured to represent prenatal smoke exposure. CpG loci that demonstrated a statistically significant difference in methylation were validated by methylation-dependent fragment separation (MDFS). Differential methylation in three genes (TSLP, GSTT1, and CYB5R3) was identified through the screen.
Among these, only thymic stromal lymphopoietin (TSLP) gene displayed significant difference in promoter methylation percentage after being validated by MDFS (p = 0.018). TSLP gene was further investigated in a larger sample of 150 children from the cohort who completed the follow-up study. Methylation status of the TSLP 5′-CpG island (CGI) was found to be significantly associated with prenatal smoke exposure (OR=3.17, 95% CI=1.63–6.19) and with AD (OR=2.32, 95% CI=1.06–5.11). The degree of TSLP 5′CGI methylation inversely correlated with TSLP protein expression levels (r = −0.45, P = 0.001).
Conclusions & Clinical Relevance
The effect of prenatal tobacco smoke exposure on the risk for AD may be mediated through DNA methylation.