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Asthma is associated with single-nucleotide polymorphisms in ADAM33.
Clin. Exp. Allergy 34, 26-31 (2004)
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.
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Anmerkungen
Besondere Publikation
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
ADAM33; association study; asthma; bronchial hyper-responsveness; case-control; family study
Sprache
englisch
Veröffentlichungsjahr
2004
HGF-Berichtsjahr
0
ISSN (print) / ISBN
0954-7894
e-ISSN
1365-2222
Zeitschrift
Clinical & Experimental Allergy
Quellenangaben
Band: 34,
Heft: 1,
Seiten: 26-31
Verlag
Wiley
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology (EPI)
PSP-Element(e)
FE 73922
Erfassungsdatum
2004-07-08