engleski

Polymorphisms in 17q12-21 region interact with pet exposure in relation to asthma presence and asthma severity

Background: Polymorphisms in 17q12-21 region are associated with asthma across different populations, but possible geneenvironment interactions have rarely been investigated. We sought to investigate the possible interaction between genes in this region and pet (cat and dog) ownership amongst Croatian schoolchildren. Method: In a case-control study, we recruited 423 children with asthma and 414 controls aged 5–18 years. Fifty-one haplotype tagging SNPs in 17q12-21 were genotyped, including polymorphisms in six genes (GSDMA, GSDMB, ORMDL3, IKZF3, ZPBP2 and TOP2). Data on pet ownership was collected using a validated questionnaire. Amongst asthmatic children, information on hospital admission due to severe asthma exacerbations was extracted from hospital notes. All asthma cases underwent spirometry. Results: There were significant interactions between 2 GSDMA SNPs (rs921651 and rs8077456) and current pet ownership in relation to asthma presence. For one of these SNPs (rs921651), there was also an interaction with pet ownership during the first year of life, in that A allele homozygotes had significantly lower risk for asthma if they kept pet in home, with no effect of early-life pet ownership among G allele carriers. Amongst children with asthma, three SNPs in ORMDL3 (rs3744246, rs4795403, rs4795404) significantly interacted with current pet ownership in relation to asthma severity (hospital admissions with asthma exacerbation). For example, carriers of the T allele of rs4795403 were at significantly higher risk of hospital admission with acute asthma exacerbation if they currently had a pet, with no effect of current pet ownership amongst C allele homozygotes. Amongst patients with asthma, we observed one significant interaction in relation to lung function (FEV1% predicted), in that T allele carriers in IKZF3 SNP rs9635726 had significantly better lung function if exposed to pets in early life, with no effect of pet ownership among C allele homozygotes. Conclusion: Polymorphisms in 17q12-21 region interact with pet exposure in relation to both asthma presence and asthma severity.

Region 17q; pet exposure; asthma

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