Acute and chronic lung function responses to salmeterol and salmeterol plus fluticasone propionate in relation to Arg16Gly β₂-adrenergic polymorphisms^*

ABSTRACT

Objective: There is conflicting clinical evidence describing the response to long-acting beta-agonist (LABA) bronchodilators for patients with Arg16Gly β₂-adrenergic receptor (ADRB2 ) genotype differences. Furthermore, the role of inhaled corticosteroids (ICS) in modulating Arg16Gly clinical responses is not well understood. The objective of this study was to investigate the effects of Arg16Gly polymorphism on the 12 hour post-dose bronchodilator response to the LABA salmeterol (SAL) or SAL plus fluticasone propionate (FSC) on first administration and following 12 weeks of treatment.

Research design and methods: Genotyping was retrospectively performed in patients with persistent asthma randomized to SAL or FSC who were participating in three similar double-blind clinical trials of 12 week duration. The primary outcome was area under the curve (AUC) for 12 hour serial FEV₁ by treatment and Arg16Gly genotype, recorded on Day 1 and Week 12. In addition, other single nucleotide polymorphisms (SNPs) associated with asthma outcomes we assessed at positions −47, +79 and +491 as well as common ADRB2 haplotypes.

Results: No statistically significant associations between Arg16Gly genotypes and serial FEV₁ clinical responses to SAL and FSC were observed following acute assessment. In addition, the FEV₁ response was preserved following 12 weeks of treatment with SAL and FSC and was not altered by Arg16Gly genotypes analyzed. These results may not be generalizable to other ethnic groups since they are derived predominantly from Caucasians.

Conclusions: In subjects with persistent asthma, the ADRB2 Arg16Gly polymorphism does not alter lung function responses to SAL or FSC over the 12 hour dosing interval following acute and chronic dosing.

Key words: :

• Asthma
• β-adrenergic receptor
• Genetics
• Long-acting beta-agonists
• Polymorphisms
• Salmeterol

Acknowledgments

Declaration of interest: S.W.Y., H.G.O., L.D.E., and W.H.A. are employees of GlaxoSmithKline. M.K. was an employee of GlaxoSmithKline at the time of the study.

Notes

* This work was presented as a poster at the ATS International Conference, Orlando, FL, USA, May 2004