engleski

Polymorphisms in 17q12-21 are associated with asthma exacerbation and lung function in asthmatic children

INTRODUCTION: More than 15 studies associated genetic variants in 17q21 region with asthma. We aimed to investigate whether amongst Croatian asthmatic children, genetic variants in this region are associated with asthma severity and exacerbation. MATERIALS AND METHODS: We recruited 423 children aged 6-18 years with physician- diagnosed asthma. Information on hospital admission with asthma exacerbations was retrieved from medical records. Data on wheeze frequency and environmental tobacco smoke (ETS) exposure was collected using validated questionnaire. Lung function (FEV1%predicted) was measured using spirometry. We analyzed 35 haplotype-tagging SNPs in 17q21. RESULTS: We found significant associations between 4 SNPs and hospital admissions (rs12150079, rs7212938, rs2290400, rs8067378). For example, G allele homozygotes in rs12150079 were at higher risk of being admitted to hospital than carriers of A allele (aOR 1.85, 95%CI 1.26-2.72, p=0.002) ; this SNP was also associated with current wheezing. Six SNPs were associated with lung function (rs9635726, rs921651, rs9900538, rs3169572, rs4795403, rs471692). In addition, we observed significant interaction between 3 SNPs (rs12603332, rs8067378, rs9303277) and in utero ETS exposure in relation to lung function (pint<0.04), in that amongst children of mothers who smoked during pregnancy, major allele homozygotes had lower FEV1%predicted than minor allele carriers, but amongst non- exposed children there was no difference in lung function between different genotype groups. DISCUSSION: Among Croatian schoolchildren with asthma variants in 17q12-21 region are associated with disease severity. We have identified a significant interaction between genetic variants and in utero tobacco smoke exposure, with lung function being diminished in specific genotypes, but only amongst children exposed to ETS.

polymorphisms; asthma; children

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