title: Pet keeping and tobacco exposure influence CD14 methylation in childhood.
abstract: BACKGROUND
  Several CD14 gene-environment interactions in relation to the development of allergic diseases have been reported, but the underlying biological mechanisms are unclear. We recently showed that CD14 methylation increased during childhood, parallelling a decreased impact of CD14 polymorphisms on soluble CD14 levels. Here, we aim to explore whether environmental stimuli during childhood affects CD14 methylation, thereby providing a biological mechanism through which environment may modulate genetic effect.
  
  
  METHODS
  CD14 methylation levels were quantified in 157 children from the prospective Environment and Childhood Asthma birth cohort at ages 2 and 10. Associations between CD14 methylation levels and house dust levels of endotoxin, β(1,3)-glucans (at 2 yr only), allergens (dog, cat, and house dust mite), pet keeping and tobacco smoke exposure (TSE; questionnaire data) at 2 and 10 yr were explored.
  
  
  RESULTS
  Children in homes without pets had larger increases in CD14 methylation through childhood (2-10 yr) compared with children with pets (2.1% increase (p = 0.003) vs. 0.4% decrease (n.s.), global p = 0.04). At 10 yr of age, lower CD14 methylation values were found in children with pets compared with children without pets at both 2 and 10 yr (5.4% vs. 7.5% [p = 0.02]). A similar trend was detected for TSE; children not exposed show larger increases in CD14 methylation, most pronounced in school-age girls exposed vs. not exposed to tobacco (5.5% vs. 7.5% methylation, p = 0.037).
  
  
  CONCLUSIONS
  Pet keeping and TSE appears to limit increase in CD14 methylation from 2 to 10 yr of age. This may partly explain the diverging CD14 allele associations with allergic diseases detected in different environments.
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, Oslo, Norway. moncmk@gmail.com
authors.forename: Monica Cheng
authors.initials: MC
authors.lastname: Munthe-Kaas
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Bertelsen
authors.forename: Tale Maehre
authors.initials: TM
authors.lastname: Torjussen
authors.forename: Hanne Sagsveen
authors.initials: HS
authors.lastname: Hjorthaug
authors.forename: Dag E
authors.initials: DE
authors.lastname: Undlien
authors.forename: Robert
authors.initials: R
authors.lastname: Lyle
authors.forename: Kristina
authors.initials: K
authors.lastname: Gervin
authors.forename: Berit
authors.initials: B
authors.lastname: Granum
authors.forename: Petter
authors.initials: P
authors.lastname: Mowinckel
authors.forename: Kai Håkon
authors.initials: KH
authors.lastname: Carlsen
authors.forename: Karin C Lødrup
authors.initials: KC
authors.lastname: Carlsen
mesh_terms: D000485:Allergens / Q000009:adverse effects; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D002415:Cats; D002648:Child; D002675:Child, Preschool; D004285:Dogs; D057890:Epigenomics; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000235:genetics*; D008297:Male; D008745:Methylation; D057805:Pets; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D000485:Allergens; D018950:Lipopolysaccharide Receptors; D014028:Tobacco Smoke Pollution