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- PMID: 23622005
- UKPMCID: 23622005
- DOI: 10.1016/j.anai.2013.01.021
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17q12-21 and asthma: interactions with early-life environmental exposures.
Blekic, Mario; Kljaic Bukvic, Blazenka; Aberle, Neda; Marinho, Susana; Hankinson, Jenny; Custovic, Adnan; Simpson, Angela
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2013;110(5):347-353.e2.
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Full-text held externally
- PMID: 23622005
- UKPMCID: 23622005
- DOI: 10.1016/j.anai.2013.01.021
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. CONCLUSION: 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.