title: 17q12-21 and asthma: interactions with early-life environmental exposures.
abstract: BACKGROUND
  17q12-21 polymorphisms are associated with asthma presence and severity across different populations.
  
  
  OBJECTIVE
  To extensively investigate the genes in this region among Croatian schoolchildren in a case-control study, taking account of early-life environmental exposures.
  
  
  METHODS
  We included 423 children with asthma and 414 controls aged 5 to 18 years. Fifty-one haplotype tagging single-nucleotide polymorphisms (SNPs) were genotyped (GSDMA, GSDMB, ORMDL3, IKZF3, ZPBP2, and TOP2). Data on exposure to smoking and furry pet ownership were collected using a validated questionnaire. Information on severe asthma exacerbations with hospital admission were retrieved from hospital notes. All patients underwent spirometry.
  
  
  RESULTS
  We found 2 SNPs (1 novel rs9635726 in IKZF3) to be associated with asthma. Among children with asthma, 4 SNPs (in ZPBP2, GSDMB, and GSDMA) were associated with hospital admissions and 8 SNPs with lung function. One SNP (rs9635726) remained significantly associated with a predicted forced expiratory volume in 1 second after false discovery rate correction. Nine markers across 5 genes showed interaction with early-life environmental tobacco smoke (ETS) exposure in relation to asthma and 2 with furry pet ownership. Among children with asthma, we observed significant interactions between early-life ETS exposure and 3 SNPs for lung function and among early-life ETS exposure, 3 SNPs (in ORMDL3 and GSDMA), and hospital admission with asthma exacerbation. Three SNPs (in ORMDL3) interacted with current furry pet ownership in relation to hospital admissions for asthma exacerbation.
  
  
  CONCLUSIONS
  Our results indicate that several genes in the 17q12-21 region may be associated with asthma. This study confirms that environmental exposures may need to be included into the genetic association studies.
authors.affiliation: General Hospital Dr Josip Bencevic Slavonski Brod, University of Osijek, Osijek, Croatia.
authors.forename: Mario
authors.initials: M
authors.lastname: Blekic
authors.forename: Blazenka
authors.initials: B
authors.lastname: Kljaic Bukvic
authors.forename: Neda
authors.initials: N
authors.lastname: Aberle
authors.forename: Susana
authors.initials: S
authors.lastname: Marinho
authors.forename: Jenny
authors.initials: J
authors.lastname: Hankinson
authors.forename: Adnan
authors.initials: A
authors.lastname: Custovic
authors.forename: Angela
authors.initials: A
authors.lastname: Simpson
mesh_terms: D000293:Adolescent; D000818:Animals; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D057805:Pets / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D014028:Tobacco Smoke Pollution