Asthma is associated with single-nucleotide polymorphisms in ADAM33

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Item Type:	Article
Title:	Asthma is associated with single-nucleotide polymorphisms in ADAM33
Creators Name:	Werner, M., Herbon, N., Gohlke, H., Altmüller, J., Knapp, M., Heinrich, J. and Wjst, M.
Abstract:	BACKGROUND: The ADAM33 gene has recently been associated with asthma and bronchial hyper-reactivity. It codes for a disintegrin and metalloproteinase that triggers intra- and extracellular signalling by protein shedding. OBJECTIVE: We examined whether polymorphisms in ADAM33 are associated with asthma and related traits in two German populations. METHODS: We genotyped 15 intragenic single-nucleotide polymorphisms (SNPs) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of allele-specific primer extension products. The transmission disequilibrium test was used for association analysis in the German asthma family study. Additionally, we tested for association of these SNPs in a case-control sample from the European Community Respiratory Health Study using Armitage's trend test. RESULTS: In both studies, we found SNPs that were significantly associated with asthma and related traits. In the family study, significant associations were observed for the SNPs F+1, ST+4 and ST+5 (with the lowest P-value for F+1, P=0.005). Remarkably, this association is seen even in the absence of linkage with two microsatellite markers from a previous genome scan either 3.1 million bases (Mb) up- or 5.6 Mb downstream. In the case-control study, SNP ST+7 (P=0.008) was significantly associated with asthma. Some of these SNPs overlapped with those found to be associated with elevated total IgE levels and bronchial hyper-responsiveness. CONCLUSION: This study replicates the recently published association between asthma and ADAM33 gene variants. However, most of the associated SNPs were at non-identical positions in the German, UK and US samples. As linkage disequilibrium is high among the tested SNPs, and there is no known functional polymorphism, either not-tested variants in ADAM33, unknown regulatory elements or a gene in close proximity is responsible for this association.
Keywords:	ADAM33, Association Study, Asthma, Bronchial Hyper-Responsiveness, Case-Control, Family Study
Source:	Clinical and Experimental Allergy
ISSN:	0954-7894
Publisher:	Blackwell Publishing
Volume:	34
Number:	1
Page Range:	26-31
Date:	January 2004
Official Publication:	https://doi.org/10.1111/j.1365-2222.2004.01846.x
PubMed:	View item in PubMed

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