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agonist use: influence
of 2 adrenoceptor polymorphism
a Department of
Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New
Zealand, b Department of Preventive and Social Medicine, c Canterbury Respiratory
Research Group, Christchurch School of Medicine, University of Otago,
Christchurch, New Zealand, d Pulmonary
and Critical Care Division, Department of Medicine, Brigham and
Women's Hospital and Harvard Medical School, Boston, Massachusetts,
USA
Correspondence to: Dr D R Taylor email: robin.taylor{at}stonebow.otago.ac.nz
Received 6 December 1999; Returned to authors 10 February 2000; Revised version received 4 April 2000; Accepted for publication 26 May 2000
BACKGROUND
Polymorphisms
of the 
2 adrenoceptor influence receptor function in
vitro and asthma phenotypes in vivo. However, their importance in
determining responses to inhaled agonist treatment has not been
clearly defined.
METHODSIn a
retrospective analysis of previously published data we have examined
relationships between polymorphisms at codons 16 and 27 of the
2 adrenoceptor and clinical outcomes in a randomised, placebo controlled, crossover trial of regularly scheduled salbutamol and salmeterol in 115 patients with mild to moderate asthma. Genotyping was obtained for positions 16 and 27 in 108 and 107 patients, respectively. For position 16, 17 patients (16%) were homozygous Arg-Arg, 40 (37%) were heterozygous Arg-Gly, and 51 (47%) were homozygous Gly-Gly.
RESULTSWithin the
homozygous Arg-16 group major exacerbations were more frequent during
salbutamol treatment than with placebo (1.91 (95% CI 1.07 to 3.12) per
year versus 0.81 (95% CI 0.28 to 1.66) per year; p = 0.005). No
significant treatment related differences occurred for heterozygous
Arg-Gly patients (salbutamol 0.11 (95% CI 0.01 to 0.40), placebo 0.54 (95% CI 0.26 to 1.00) exacerbations per year) or homozygous Gly-16
patients (salbutamol 0.38 (95% CI 0.17 to 0.73), placebo 0.30 (95% CI
0.12 to 0.61) exacerbations per year). No adverse changes occurred for
any position 16 subgroup with salmeterol. There was no significant
relationship between position 27 genotypes and treatment related outcomes.
CONCLUSIONHomozygous
Arg-16 patients are susceptible to clinically important increases in
asthma exacerbations during chronic dosing with the short acting
2 agonist salbutamol.
2 adrenoceptor;
genotype;
polymorphism;
asthma;
salbutamol;
salmeterol
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