title: Prenatal smoke exposure, DNA methylation, and childhood atopic dermatitis.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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
  The effect of prenatal tobacco smoke exposure on the risk for AD may be mediated through DNA methylation.
authors.affiliation: Department of Pediatrics, Taipei Hospital Department of Health, Taipei, Taiwan.
authors.forename: I-J
authors.initials: IJ
authors.lastname: Wang
authors.forename: S-L
authors.initials: SL
authors.lastname: Chen
authors.forename: T-P
authors.initials: TP
authors.lastname: Lu
authors.forename: E Y
authors.initials: EY
authors.lastname: Chuang
authors.forename: P-C
authors.initials: PC
authors.lastname: Chen
mesh_terms: D002648:Child; D018899:CpG Islands; D042966:Cytochrome-B(5) Reductase / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D019175:DNA Methylation; D003876:Dermatitis, Atopic / Q000209:etiology*; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; C583417:CYB5R3 protein, human; D042966:Cytochrome-B(5) Reductase; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D000094632:Thymic Stromal Lymphopoietin