Article date: January 2004
By: Daniel K. C. Lee, Caroline E. Bates, Brian J. Lipworth, in Volume 57, Issue 1, pages 100-104
Aims The relationship between β2‐adrenoceptor polymorphisms at positions 16 and 27, and the acute systemic β2‐adrenoceptor effects of inhaled salbutamol is unclear. We therefore elected to evaluate the influence of common homozygous β2‐adrenoceptor haplotypes on the acute systemic β2‐adrenoceptor effects following inhaled salbutamol in asthmatic subjects.
Methods An initial database search of 531 asthmatic subjects identified the two commonest homozygous haplotypes at positions 16 and 27 to be Arg16‐Gln27 (12%) and Gly16‐Glu27 (19%). After a 1‐week washout period where all β2‐adrenoceptor agonists were withdrawn, 16 Caucasian subjects (Arg16‐Gln27: n = 8 and Gly16‐Glu27: n = 8) were given a single dose of inhaled salbutamol (1200 µg), followed by serial blood sampling for serum potassium, along with measurements of diastolic blood pressure and heart rate, at 5‐min intervals for 20 min.
Results The two groups were well matched for age, sex, FEV1, and inhaled corticosteroid dose. Baseline values for serum potassium, diastolic blood pressure and heart rate were not significantly different comparing Arg16‐Gln27 vs Gly16‐Glu27. The mean ± SEM maximum serum potassium change from baseline over 20 min was significantly greater (P = 0.04) for Arg16‐Gln27: −0.37 ± 0.05 mmol l−1vs Gly16‐Glu27: −0.23 ± 0.04 mmol l−1; 95% CI for difference: −0.01 to −0.28 mmol l−1. The maximum diastolic blood pressure change from baseline over 20 min was significantly greater (P = 0.0008) for Arg16‐Gln27: −13 ± 1 mmHg vs Gly16‐Glu27: −4 ± 2 mmHg; 95% CI for difference: −5, 14 mmHg. There was no significant difference comparing the maximum heart rate change from baseline for Arg16‐Gln27: 10 ± 3 beats min−1vs Gly16‐Glu27: 10 ± 3 beats min−1.
Conclusions Caucasian asthmatic subjects with the Arg16‐Gln27 haplotype exhibited a greater systemic response to inhaled salbutamol, compared with those with the Gly16‐Glu27 haplotype. The attenuated β2‐adrenoceptor response in the Gly16‐Glu27 haplotype would be in keeping with increased susceptibility to prior down‐regulation by endogenous catecholamines.
DOI: 10.1046/j.1365-2125.2003.01978.x
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