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ADAM33 Polymorphisms, environmental tobacco smoke exposure and childhood asthma in Croatia

Background: Little is known about genetic associates of asthma in Croatia. A disintegrin and metalloproteinase 33 (ADAM33) was the first asthma susceptibility gene to be discovered by positional cloning. Significant associations have previously been reported between single nucleotide polymorphisms (SNPs) in ADAM33 and asthma in ethnically diverse populations. We investigated the association between ADAM33 SNPs and asthma amongst Croatian schoolchildren and interactions with environmental tobacco smoke (ETS) exposure. Methods: 424 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 ; 415 non-asthmatic controls were randomly selected from non-asthmatic children attending the outpatient department or local schools. ETS exposure was ascertained by validated questionnaire. We genotyped 32 haplotype tagging SNPs in ADAM33 (Sequenom). Results: All SNPs were in Hardy-Weinberg equilibrium (p>0.01). We found a significant association between nine SNPs and asthma (p<0.03). For two of these SNPs (rs487377 and rs 2485700), there was a significant interaction between genotype and ETS exposure. In the multivariate analysis for rs2485700 (adjusted for gender), we found a statistically significant interaction between the genotype and ETS exposure (p=0.03), in that the risk of asthma was increased amongst carriers of the minor allele, but only amongst smokers (aOR 2.1, 95% CI 1.4- 3.2, p<0.001), with no increase in risk amongst non- smokers (0.9, 0.5-1.8, p=0.9). Similarly, in the multivariate analysis for rs487377 (adjusted for gender), we found a statistically significant interaction between the genotype and ETS exposure (p=0.04), with the risk of asthma increasing amongst the minor allele homozygotes amongst smokers (3.7, 1.5-9.4, p=0.006), but not amongst non-smokers (0.8, 0.2-2.6, p=0.7). Conclusions: Variants in ADAM33 were associated with asthma in Croatian schoolchildren. In addition, we have identified significant interaction between genotype and ETS exposure, with the risk of asthma increasing in specific genotypes only amongst children exposed to ETS.

ADAM33 ; asthma ; environmental tobacco smoke

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