Asthma is associated with single-nucleotide polymorphisms in ADAM33

Clin Exp Allergy. 2004 Jan;34(1):26-31. doi: 10.1111/j.1365-2222.2004.01846.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins
  • Adult
  • Asthma / diagnosis
  • Asthma / genetics*
  • Bronchial Provocation Tests
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Genetic Predisposition to Disease
  • Genotype
  • Germany
  • Humans
  • Likelihood Functions
  • Metalloendopeptidases / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • ADAM Proteins
  • ADAM33 protein, human
  • Metalloendopeptidases