Genetic Variation of the BETA-2 Adrenergic Receptor and the Bronchodilatory Response to Albuterol in Patients with Cystic Fibrosis

Abstract

Specific Aims: We sought to determine the influence of genetic variation of ADRB2 on the airway response to albuterol in patients with CF when compared to matched healthy controls at baseline and at 60 minutes following the administration of albuterol (2.5mg diluted in 3ml normal saline). Methods: Baseline pulmonary function (forced vital capacity, FVC, forced expiratory flow in 1-second, FEV1, mid-maximal expiratory flow, MMF, and forced expiratory flow at 50% of the FVC) was assessed in 17 patients with CF and 31 healthy subjects. Main Results: As expected, the healthy group had higher baseline pulmonary function when compared to the CF group (FVC=97±3 vs. 83±5; FEV1=95±3 vs. 72±6; MMF=90±4 vs. 54±8, % predicted for healthy and CF, respectively, mean±SE, p<0.05 for all. We compared Arg16Arg to Arg16Gly/Gly16Gly subjects. There was no effect of genotype on the response to albuterol in healthy subjects. However, in the CF group, we found that the Arg16Arg group (n=6) had an attenuated response to β-agonist when compared to the Gly-containing group (n=11) (FVC=0±0.9 vs. 6±3: FEV1=3±1 vs. 7±4: MMF=12±3 vs. 12±5 % change, for Arg16Arg and Gly-containing groups, respectively, p<0.05 for FVC, p=0.06 for FEV1). Conclusions: These results demonstrate a differential response to β-agonists according to genetic variation of the ADRB2 at amino acid 16. Due to the differences in FVC and FEV1 but not in MMF, these data suggest that the genetic difference in airway function is primarily in bronchodilation of the larger airways.