title: Interaction of a 17q12 variant with both fetal and infant smoke exposure in the development of childhood asthma-like symptoms.
abstract: BACKGROUND
  Gene variants on chromosome 17q12-21 are associated with an increased risk of childhood-onset asthma, a risk known to be modified by environmental tobacco smoke (ETS).
  
  
  OBJECTIVE
  To assess whether the association of rs2305480 on chromosome 17q12 in the GSDML gene with asthma-like symptoms in the first 4 years of life is modified by smoke exposure during fetal and early postnatal life.
  
  
  METHODS
  We used data from two independent prospective cohort studies from fetal life onwards in the Netherlands. We genotyped rs2305480 and assessed maternal smoking during pregnancy and ETS exposure at the age of 2. Asthma-like symptoms, defined as any reported wheezing, shortness of breath or dry nocturnal cough, were reported by parents when the children were 1, 2, 3, and 4 years. Analyses were based on a total group of 4461 Caucasian children.
  
  
  RESULTS
  The G risk-allele of rs2305480 was associated with asthma-like symptoms [overall odds ratio 1.17 (1.11, 1.24), 2.66E-9]. The effect of rs2305480 on asthma-like symptoms was stronger among children who were exposed to smoke during fetal life (P-interaction = 0.04). Smoke exposure in early postnatal life was also associated with an increased effect of the 17q12 single nucleotide polymorphism (SNP) on asthma-like symptoms (P-interaction = 5.06E-4). These associations were consistent in both cohorts.
  
  
  CONCLUSIONS
  A 17q12 variant, rs2305480, was associated with asthma-like symptoms in preschool children, and this association was modified by smoke exposure already during fetal life, and in infancy. Further investigation regarding SNPs in linkage disequilibrium with rs2305480 in relation to pathophysiological pathways is needed.
authors.affiliation: The Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: R J P
authors.initials: RJ
authors.lastname: van der Valk
authors.forename: L
authors.initials: L
authors.lastname: Duijts
authors.forename: M
authors.initials: M
authors.lastname: Kerkhof
authors.forename: S P
authors.initials: SP
authors.lastname: Willemsen
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: H A
authors.initials: HA
authors.lastname: Moll
authors.forename: H A
authors.initials: HA
authors.lastname: Smit
authors.forename: B
authors.initials: B
authors.lastname: Brunekreef
authors.forename: D S
authors.initials: DS
authors.lastname: Postma
authors.forename: V W V
authors.initials: VW
authors.lastname: Jaddoe
authors.forename: G H
authors.initials: GH
authors.lastname: Koppelman
authors.forename: J C
authors.initials: JC
authors.lastname: de Jongste
mesh_terms: D000328:Adult; D001249:Asthma / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D005333:Fetus; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009426:Netherlands; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D014028:Tobacco Smoke Pollution