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Ann Allergy Asthma Immunol. 2013 May;110(5):347-353.e2. doi: 10.1016/j.anai.2013.01.021. Epub 2013 Mar 6.

17q12-21 and asthma: interactions with early-life environmental exposures.

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  • 1General Hospital Dr Josip Bencevic Slavonski Brod, University of Osijek, Osijek, Croatia.

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.

Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

[PubMed - indexed for MEDLINE]
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