Abstract
BackgroundADAM33, the first asthma candidate gene identified by positional cloning, may be associated with childhood asthma, lung function decline and bronchial hyperresponsiveness. However, replication results have been inconclusive in smaller previous study populations probably due to inconsistencies in asthma phenotypes or yet unknown environmental influences. Thus, we tried to further elucidate the role of ADAM33 polymorphisms (SNPs) in a genetic analysis of German case control and longitudinal populations.MethodsUsing MALDI-TOF, ten ADAM33 SNPs were genotyped in 1,872 children from the International Study of Asthma and Allergy in Childhood (ISAAC II) in a case control setting and further 824 children from the longitudinal cohort Multicentre Study of Allergy (MAS). In both populations the effects of single SNPs and haplotypes were studied and a gene environment analysis with passive smoke exposure was performed using SAS/Genetics.ResultsNo single SNP showed a significant association with doctor's diagnosis of asthma. A trend for somewhat more profound effects of ADAM33 SNPs was observed in individuals with asthma and BHR. Haplotype analyses suggested a minor effect of the ADAM33 haplotype H4 on asthma (p = 0.033) but not on BHR. Associations with non atopic asthma and baseline lung function were identified but no interaction with passive smoke exposure could be detected.ConclusionThe originally reported association between ADAM33 polymorphisms and asthma and BHR could not be confirmed. However, our data may suggest a complex role of ADAM33 polymorphisms in asthma ethiology, especially in non atopic asthma.
Highlights
ADAM33, the first asthma candidate gene identified by positional cloning, may be associated with childhood asthma, lung function decline and bronchial hyperresponsiveness
ADAM33, a disintegrin and metalloproteinase 33 has been the first gene published, which had been identified by positional cloning as a putative candidate gene for the development of asthma and bronchial hyperresponsiveness [1]
It may be more relevant in adult or non-atopic than in atopic asthma. It may affect lung function more than atopy status. Environmental factors such as passive smoke exposure could potentially interact with ADAM33 in exerting its remodeling function in the lung as ADAM33 seems to be involved in COPD mediated processes[8]
Summary
ADAM33, the first asthma candidate gene identified by positional cloning, may be associated with childhood asthma, lung function decline and bronchial hyperresponsiveness. Ever since the first report of association between ADAM33 polymorphisms and asthma in two Caucasian populations from the UK and the USA, a number of replication studies have been published with very diverse results. It can be hypothesized that ADAM33, involved in remodeling, may be especially important in some specific forms of asthma. It may be more relevant in adult or non-atopic than in atopic asthma. It may affect lung function more than atopy status. Environmental factors such as passive smoke exposure could potentially interact with ADAM33 in exerting its remodeling function in the lung as ADAM33 seems to be involved in COPD mediated processes[8]
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