engleski

Genetic polymorphisms in the region 20p13 and asthma among Croatian schoolchildren

BACKGROUND: Since the first report of association between polymorphisms in ADAM33 with asthma and bronchial hyperresponsiveness, there have been a number of replications studies with diverse results. Possible explanations for the heterogeneity between the studies include the effects of other genes in the vicinity (since linkage disequilibrium in the 20p13 region is high), gene-gene and gene-environment interactions. We aimed to extensively investigate the association between genes in the 20p13 region and asthma amongst Croatian schoolchildren. METHODS: 423 children with asthma aged 6 to 18 years (cases), were recruited into the study from the local hospital if the following criteria were met: (1) physician-diagnosed asthma, (2) asthma symptoms within the previous 12 months, and (3) use of antiasthma medication ; 414 non-asthmatic controls were randomly selected from the outpatient department or local schools. Amongst asthmatic children, we retrieved the data on hospital admissions with acute asthma from the hospital notes. We genotyped 108 SNPs from 5 genes in the 20p13 region (ATRN, GFRA4, ADAM33, SIGLEC1, HSPA12B ; Sequenom). RESULTS: All SNPs were in Hardy-Weinberg equilibrium (p>0.01). We found a significant association between 18 SNPs and asthma (p<0.05) ; 7 of these 18 associations passed the correction for multiple testing (3 in ATRN, 3 in ADAM33 and 1 in HSPA12B). In addition, amongst children with asthma, homozygotes for minor allele (C) of rs609203 in SIGLEC1 were significantly more likely to ever have been admitted to hospital with acute exacerbation of asthma (aOR 2.7, 95%CI 1.01- 7.25, p<0.05). CONCLUSION: Our results suggest that other genes in the vicinity of ADAM33 may play a role in the pathogenesis of asthma. Furthermore, we found a significant association between severe asthma exacerbations and a variant in SIGLEC1.

region 20p ; childhood asthma

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