title: Beta2 adrenergic receptor (ADRβ2) haplotype pair (2/4) is associated with severe asthma.
abstract: BACKGROUND
  β2 adrenergic receptor (ADRβ2) polymorphisms including ADRβ2+46G>A have been reported to cause adverse outcomes in mild asthmatics. The extent to which ADRβ2 polymorphisms and in particular their haplotypes contribute to severe asthma is unknown.
  
  
  OBJECTIVE
  To determine the association of ADRβ2 polymorphisms and haplotypes with asthma severity.
  
  
  METHODS
  Caucasians (n = 2979) were genotyped for 11 ADRβ2 polymorphisms. The cohort (mean age 39.6, 60% female) included 2296 non-asthmatics, 386 mild asthmatics, 172 moderate asthmatics and 125 severe asthmatics. Haplotype frequency and haplotype pair for each subject was determined using the PHASE algorithm.
  
  
  RESULTS
  The three asthmatic cohorts were comparable in age and gender but were distinguishable from each other in terms of symptoms, spirometry, medication use and health care utilisation (p <0.001). None of the polymorphisms showed a genotypic or allelic association with asthma diagnosis or severity. Nine haplotypes were identified and no association was found with asthma diagnosis or severity per se. Haplotype pair 2/4 was associated with asthma severity (Trend Test, OR 1.42, p = 0.0008) but not with asthma per se. Prevalence of haplotype pair 2/2 appeared to decrease with asthma severity (Trend Test, OR 0.78, p = 0.067). Two new haplotypes were identified, occurring exclusively in asthmatics at a frequency of ≥ 1%. In addition, a positive association between carriage of ADRβ2 +523*C and increased risk of atopy was discovered.
  
  
  CONCLUSIONS
  ADRβ2 haplotype pair 2/4 is associated with severe asthma and is consistent with findings of poor bronchodilator response in mild asthmatics who are also haplotype 2/4.
authors.affiliation: Molecular Genetics and Inflammation Unit, Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Crawley, Nedlands, Western Australia, Australia; School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia; Department of Respiratory Medicine, Royal Perth Hospital, Perth, Western Australia, Australia.
authors.forename: Li Ping
authors.initials: LP
authors.lastname: Chung
authors.affiliation: Molecular Genetics and Inflammation Unit, Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Crawley, Nedlands, Western Australia, Australia; School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Baltic
authors.affiliation: The Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ferreira
authors.affiliation: Molecular Genetics and Inflammation Unit, Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Crawley, Nedlands, Western Australia, Australia; School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Suzanna
authors.initials: S
authors.lastname: Temple
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia; Department of Respiratory Medicine, Royal Perth Hospital, Perth, Western Australia, Australia.
authors.forename: Grant
authors.initials: G
authors.lastname: Waterer
authors.affiliation: Molecular Genetics and Inflammation Unit, Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Crawley, Nedlands, Western Australia, Australia; School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001249:Asthma / Q000235:genetics* / Q000473:pathology; D001993:Bronchodilator Agents / Q000008:administration & dosage; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D013147:Spirometry
chemical_list: D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2