Beta 2 adrenergic receptor polymorphisms in cystic fibrosis.

There has been a recent emphasis on identifying modifier genes that influence the severity of cystic fibrosis (CF) lung disease. The beta-2-adrenergic receptor is expressed on airway smooth muscle, is the target for inhaled beta agonists, and has several common polymorphisms in its gene, ADRB2. Polymorphisms changing glycine to arginine or glutamate to glutamine in codons 16 and 27, respectively, were associated with differences in clinical response to inhaled beta agonists in individuals with asthma. We compared acute airway responsiveness and 5-year decline in pulmonary function in CF patients with different ADRB2 genotypes. One hundred and six subjects performed spirometry before and after the administration of an inhaled bronchodilator, and had ADRB2 genotype determined for codons 16 and 27. Comparing the percent change in FEV(1) and FEF(25-75) continuously revealed differences in the degree of airway responsiveness to bronchodilator between ADRB2-genotyped groups. However, there was no significant relationship between the ADRB2 genotype at positions 16 and 27 and bronchodilator response when defined as 12% improvement in FEV(1). Five-year decline in percent predicted FEV(1) showed no association with ADRB2 genotype. These data are consistent with variants of the ADRB2 gene having different responses to bronchodilator, but the long-term effects, if any, are not apparent over a 5-year period.