Beta2 adrenergic receptor (ADRβ2) haplotype pair (2/4) is associated with severe asthma.

Autor: Chung LP; 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., Baltic S; 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., Ferreira M; The Queensland Institute of Medical Research, Brisbane, Queensland, Australia., Temple S; 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., Waterer G; School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia; Department of Respiratory Medicine, Royal Perth Hospital, Perth, Western Australia, Australia., Thompson PJ; 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.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2014 Apr 01; Vol. 9 (4), pp. e93695. Date of Electronic Publication: 2014 Apr 01 (Print Publication: 2014).
DOI: 10.1371/journal.pone.0093695
Abstrakt: 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.
Databáze: MEDLINE
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