Aims: The relationship between beta2-adrenoceptor polymorphisms and bronchoprotective response with long-acting beta2-adrenoceptor agonists is unknown.
Methods: We retrospectively analysed data from six placebo-controlled randomized studies in corticosteroid treated asthmatics where formoterol or salmeterol were administered over a 1-2-week period, with prior 1-2 week washout, assessing the primary end point of methacholine PD20 and adenosine monophosphate PC20, following first and last dose, expressed as doubling dose difference from placebo.
Results: There was no significant heterogeneity between the different studies. Patients who had homozygous or heterozygous genotypes containing the arginine-16 polymorphism (Arg16-Arg16 or Arg16-Gly16) had greater bronchoprotective subsensitivity compared with the homozygous glycine-16 genotype (Gly16-Gly16), amounting to a mean doubling dose difference of 1.49 (95% CI 0.50, 2.48), after the last dose. Subsensitivity of response was greater with formoterol than salmeterol after the last dose in all genotypes, especially with the arginine-16 polymorphism, amounting to a doubling dose difference of 3.00 (95% CI 1.01, 4.99) between formoterol and salmeterol.
Conclusions: Our retrospective analysis showed that the arginine-16 polymorphism was associated with subsensitivity of response for bronchoprotection, which was greater for formoterol than salmeterol. A prospective study will be required in order to further evaluate these findings, particularly to assess whether these differences are mirrored by exacerbations.