title: Smoke exposure interacts with ADAM33 polymorphisms in the development of lung function and hyperresponsiveness.
abstract: BACKGROUND
  ADAM33 is the first identified asthma gene by positional cloning, especially asthma combined with bronchial hyperresponsiveness (BHR). Moreover, ADAM33 is associated with early-life lung function and decline of forced expiratory volume in 1 s (FEV(1)) in the general population. In utero and postnatal cigarette smoke exposure (CSE) are associated with reduced lung function, and development of BHR and asthma. We hypothesized that this may occur via interaction with ADAM33.
  
  
  OBJECTIVE
  To replicate the role of ADAM33 in childhood lung function and development of BHR and asthma. Furthermore, we investigated gene-environment interaction of ADAM33 with in utero and postnatal CSE in the Dutch PIAMA cohort.
  
  
  METHODS
  Six ADAM33 single-nucleotide polymorphisms (SNPs) were genotyped. Rint was measured at age 4 and 8 years, FEV(1) and BHR at age 8 years; asthma was based on questionnaire data at age 8.
  
  
  RESULTS
  In the total cohort, the rs511898 A, rs528557 C, and rs2280090 A alleles increased the risk to develop asthma (+BHR). There existed interaction between in utero but not postnatal CSE and the rs528557 and rs3918396 SNPs with respect to development of BHR, the rs3918396 SNP with Rint at age 8 and the rs528557 SNP with FEV(1)% predicted.
  
  
  CONCLUSIONS
  We confirm associations between ADAM33 and the development of asthma (+BHR). This is the first study suggesting that interaction of in utero CSE with ADAM33 results in reduced lung function and the development of BHR, which needs further confirmation.
authors.affiliation: Department of Pulmonology, University medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: N E
authors.initials: NE
authors.lastname: Reijmerink
authors.forename: M
authors.initials: M
authors.lastname: Kerkhof
authors.forename: G H
authors.initials: GH
authors.lastname: Koppelman
authors.forename: J
authors.initials: J
authors.lastname: Gerritsen
authors.forename: J C
authors.initials: JC
authors.lastname: de Jongste
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
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000502:physiology; D001249:Asthma / Q000209:etiology / Q000235:genetics; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D015810:Linkage Disequilibrium; D008168:Lung / Q000502:physiology*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects*
chemical_list: D012906:Smoke; D051722:ADAM Proteins; C450441:ADAM33 protein, human