1. ¹The Co-operative Research Centre (CRC) for Asthma, Sydney, Australia
2. ²The Asthma and Allergy Research Institute (Inc.), Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
3. ³The Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Western Australia, Australia
4. ⁴The Western Australian Institute for Medical Research and Centre for Medical Research, Perth, Australia
5. ⁵School of Public Health, Queensland University of Technology, Brisbane, Australia
6. ⁶School of Life Sciences and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
7. ⁷Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia
8. ⁸Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital and Monash University, Melbourne, Australia

Correspondence: Professor PJ Thompson, Asthma and Allergy Research Institute, Ground Floor E Block, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia. Tel: +61 (0)8 9346 3198; Fax: +61 (0)8 9346 4159; E-mail: aari@aari.uwa.edu.au

⁹These authors contributed equally to this paper

Received 22 June 2004; Revised 7 March 2006; Accepted 13 April 2006; Published online 14 June 2006.

Abstract

The ADAM33 gene has recently been identified as being a potentially important asthma candidate gene, and polymorphisms in this gene have been shown to be associated with asthma and bronchial hyperresponsiveness in Caucasian individuals from several populations. We performed chip-based matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry using the MassARRAY system and multiplexed genotyping assays to investigate the association between 10 single nucleotide polymorphisms (SNPs) in the ADAM33 gene (F_+1, Q_-1, S_1, ST_+4, ST_+7, V_-2, V_-1, V_2, V_4, V_5) and asthma and asthma severity in a large Australian Caucasian population of nonasthmatic controls (n=473), and patients with mild (n=292), moderate (n=238) and severe (n=82) asthma. No significant association was found between any one of the 10 SNPs and asthma or asthma severity, however, there was a significant global haplotypic association with asthma (P=0.0002) and disease severity (P=0.0001), driven by the combination of two key SNPs, V_-1 and ST_+7. A meta-analysis of all the genetic studies conducted to date found significant between-study heterogeneity, likely to reflect population stratification. Our analysis of ADAM33 haplotypes further suggests a likely role for ADAM33 in the asthma phenotype, although it does not exclude an association with another locus in linkage disequilibrium with ADAM33.