Associations of polymorphisms in the beta-2 adrenergic receptor in severe and mild asthmatic African-Americans

Purpose: While recent studies have demonstrated that the β₂-adrenergic receptor (β2AR) polymorphisms do not appear to cause susceptibility to asthma, they have suggested associations with differences in asthma severity, including nocturnal symptoms, bronchial hyperresponsiveness and steroid dependence. Results have been conflicting, though, and possible ethnic differences have also been reported. We, therefore, investigated whether polymorphisms at amino acid 16 and 27 of the β2AR are associated with clinically-defined severe asthma compared to mild disease in a select ethnic group. Methods: Asthmatic African-Americans, who appear to have increased asthma mortality, were chosen from ongoing asthma clinical studies and from the University of Maryland Asthma Clinic. Subjects were evaluated with pulmonary function tests, smoking history, pattern of disease, medication usage and history of asthma exacerbations. Mild asthmatics had a Forced Expiratory Volume in the first second (FEV₁) of > 80% of predicted and no prior hospitalizations; severe disease was defined as FEV₁ < 60% of predicted or frequent nocturnal symptoms and asthma exacerbations. DNA was extracted from blood samples and subjects were genotyped for alleles at two polymorphic sites (amino acid 16 and 27) by Restriction Fragment Length Polymorphism (RFLP) analysis. Results: Eighteen mild asthmatics (mean FEV₁=91% of predicted) and 36 severe asthmatics (mean FEV₁=50% of predicted) were characterized. At amino acid 16, the presence of arginine or glycine was not significantly associated with either mild or severe disease. Similarly, neither glutamine nor glutamic acid at position 27 was associated with asthma severity. Conclusions: Polymorphisms at amino acids 16 or 27 of the β2AR do not appear to be related to the severity of asthma in this population of African-Americans. Clinical Implications: Despite the relatively small sample size, this data does not suggest a major role for β2AR genotyping in assessing asthma severity. However, polymorphisms in the β2AR may still be related to responses to therapy with β2 adrenergic agonists.