The arginine‐16 β2‐adrenoceptor polymorphism predisposes to bronchoprotective subsensitivity in patients treated with formoterol and salmeterol

Article date: January 2004

By: Daniel K. C. Lee, Graeme P. Currie, Ian P. Hall, John J. Lima, Brian J. Lipworth, in Volume 57, Issue 1, pages 68-75

Aims   The relationship between β2‐adrenoceptor polymorphisms and bronchoprotective response with long‐acting β2‐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.

DOI: 10.1046/j.1365-2125.2003.01955.x

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