title: ADAM33 haplotypes are associated with asthma in a large Australian population.
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.
authors.affiliation: The Co-operative Research Centre (CRC) for Asthma, Sydney, Australia.
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Kedda
authors.forename: David L
authors.initials: DL
authors.lastname: Duffy
authors.forename: Bernadette
authors.initials: B
authors.lastname: Bradley
authors.forename: Robyn E
authors.initials: RE
authors.lastname: O'Hehir
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Thompson
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000328:Adult; D000368:Aged; D001249:Asthma / Q000209:etiology / Q000235:genetics*; D001315:Australia; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012907:Smoking; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D044465:White People / Q000235:genetics
chemical_list: D051722:ADAM Proteins; C450441:ADAM33 protein, human