Acute systemic effects of inhaled XXXX in @entity748 subjects expressing common homozygous @entity2162 haplotypes at positions 16 and 27.

@entity748 @entity2162 @entity1009 @entity3045 @entity4022 @entity228 @entity534 @entity367 @entity972 @entity2661
AIMS: The relationship between @entity2162 polymorphisms at positions 16 and 27, and the acute systemic @entity2162 effects of inhaled @entity3045 is unclear. We therefore elected to evaluate the influence of common homozygous @entity2162 haplotypes on the acute systemic @entity2162 effects following inhaled @entity3045 in @entity748 subjects. METHODS: An initial database search of 531 @entity748 subjects identified the two commonest homozygous haplotypes at positions 16 and 27 to be @entity534 16-Gln27 (12%) and @entity4022 16- @entity367 27 (19%). After a 1-week washout period where all @entity2162 agonists were withdrawn, 16 Caucasian subjects ( @entity534 16-Gln27: n = 8 and Gly16- @entity367 27: n = 8) were given a single dose of inhaled @entity3045 (1200 microg), followed by serial blood sampling for serum @entity972 , 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 @entity228 dose. Baseline values for serum @entity972 , diastolic blood pressure and heart rate were not significantly different comparing @entity534 16-Gln27 vs Gly16- @entity367 27. The mean +/- SEM maximum serum @entity972 change from baseline over 20 min was significantly greater (P = 0.04) for @entity534 16-Gln27: -0.37 +/- 0.05 mmol l(-1) vs Gly16- @entity367 27: -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 @entity534 16-Gln27: -13 +/- 1 mmHg vs Gly16- @entity367 27: -4 +/- 2 mmHg; 95% CI for difference: -5, 14 mmHg. There was no significant difference comparing the maximum heart rate change from baseline for @entity534 16-Gln27: 10 +/- 3 beats @entity1009 ) vs Gly16- @entity367 27: 10 +/- 3 beats @entity1009 ). CONCLUSIONS: Caucasian @entity748 subjects with the @entity534 16-Gln27 haplotype exhibited a greater systemic response to inhaled @entity3045 , compared with those with the @entity4022 16- @entity367 27 haplotype. The attenuated @entity2162 response in the Gly16-Glu27 haplotype would be in keeping with increased susceptibility to prior down-regulation by endogenous @entity2661 .
