PURPOSE:Some studies have reported that Arg16Gly and Gln27Glu polymorphisms in the β2-adrenergic receptor (ADRB2) are associated with modulating responses to β2-agonist therapy for asthma. We evaluated ADRB2 polymorphisms across the entire gene, for their association with asthma exacerbations in subjects treated with salmeterol (SAL) or fluticasone propionate/salmeterol via Diskus (FSC).
METHODS:Four hundred and eighty-five subjects (>12 years) entered an 8-week open-label prn albuterol run-in followed by an 8-week prn ipratropium run-in prior to randomization to 16–weeks of treatment with SAL (50mcg BID) or FSC (100/50mcg BID). Exacerbations were defined as worsening asthma requiring an ED visit, hospitalization, or medication beyond the protocol. Eleven SNPs and a poly-C repeat in the 3’ region were genotyped or sequenced.
RESULTS:Results were compared between genotypes during the combined open-label periods and between genotypes during treatment with SAL or FSC. During the 16-week open label run-in periods there was 1 statistically significant marker at position -1818 where the frequency of exacerbations was 0.010 and 0.057 (p=0.005) for the A/A and T/T genotypes respectively. For the Arg16Gly genotypes the exacerbation frequency for Arg/Arg was 0.056 vs Gly/Gly of 0.013 (p=0.057). There were no associations observed in the poly-C region when grouped by subjects with <12 repeats vs subjects with ≥12. Once subjects entered the double-blind treatment period with SAL or FSC, exacerbation frequencies markedly decreased in the FSC group, with no significant genotype effects. Similarly in the SAL treatment arm, no genotype effects were observed.
CONCLUSION:Polymorphisms in the ADRB2 do not appear to be strong predictors of asthma exacerbations. Treatment with FSC markedly decreased asthma exacerbations across all ADRB2 genotypes.
CLINICAL IMPLICATIONS:The results reported here depict the lack of pharmacogenetic associations with exacerbations, but further study is needed in higher risk populations such as African Americans and patients with severe asthma.(SFA100062).
DISCLOSURE:Wayne Anderson, Employee GSK; No Product/Research Disclosure Information