We have confirmed in this replication study that common ADRB2 genotypes or haplotypes at positions 16/27 do not influence BHR in methacholine-responsive patients with asthma.
In contrast, asthma phenotypes, such as asthma severity and bronchial hyperresponsiveness, have been associated with beta(2)-adrenoceptor polymorphisms.
Asthma models show increased ASM G(alphai) expression, considered the basis for the proasthmatic phenotypes of enhanced bronchial hyperreactivity to contraction mediated by M(3)-muscarinic receptors and diminished relaxation mediated by beta(2)-adrenergic receptors (beta(2)ARs).
The Arg16/Gln27 beta(2)AR haplotype is important in COPD, asthma and BHR, and may be associated with more severe respiratory symptoms in middle-aged and older adults.
B2AR polymorphisms may play an important role in the expression of nocturnal cough in atopic subjects but not in the expression of atopy and bronchial hyperresponsiveness in a general population.
We performed a retrospective analysis of our database (n = 487) of patients with asthma with the aim first, to compare methacholine and AMP challenge as screening tools, and second, to identify any relationships between BHR and disease severity markers or beta(2)-adrenoceptor genotype.
This observation suggests therefore that ADRB2 gene can confer genetic susceptibility to BHR, rather than having only a disease-modifying effect in asthma.
However, given the importance of beta2AR in modulating lung function, studies have been carried out to determine if polymorphic forms may play roles in promoting asthmatic phenotypes, establishing bronchial hyperreactivity, or influencing the response to acute or chronic beta-agonist therapy.