engleski

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

Background: More then 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. 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. Conclusion: Variants in 17q12-21 region may be associated with asthma severity and may interact with in utero ETS exposure in determining lung function amongst asthmatic children. 586s

17q region; lung function; smoke; childhood asthma

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