Association between beta2 adrenergic receptor (ADRβ2) haplotype pair and severe asthma in an Australian caucasian population

Background: Studies in mild asthmatics showed adverse outcomes with chronic use of short or long acting beta agonists in individuals with β2 adrenergic receptor ( ADRβ2) polymorphisms including ADRβ2 +46G>A. The extent to which ADRβ2 polymorphisms contribute to severe asthma is unknown, hence the association of ADRβ2 polymorphisms with asthma severity was investigated. Methods: Caucasians with mild (n=201) or severe asthma (n=118, defined by ATS criteria 2000) and non-asthmatics (n=200) were recruited. All subjects (mean age 53.1, 60% atopic) were genotyped for 12 ADRβ2 polymorphisms (-1023, -709, -654, -468, -367, -47, -20, +46, +79, +252, +491, +523). Haplotype frequency and haplotype pair was determined via PHASE. Results: Severe, mild and non-asthmatic cohorts were matched by age but distinguishable from each other in terms of symptoms, lung function, medication use and health care utilisation (p Conclusions: ADRβ2 haplotype pair 2/4 is associated with severe asthma. Known haplotypic difference in receptor expression and acute bronchodilator response in mild compared to severe asthmatics suggests a role for ADRβ2 haplotypes in the development and/or treatment response in severe asthmatics.