BACKGROUND: In-vitro studies have suggested that polymorphisms of the @entity2162 may influence the desensitisation induced by @entity2263 -agonists. We investigated the influence of @entity2162 polymorphism on the development of bronchodilator desensitisation in @entity565 @entity1 . METHODS: We carried out an analysis of 22 moderately severe stable asthmatics, mean age 38 years, FEV1 63% of predicted and FEF25-75 38% of predicted, who received a median inhaled corticosteroid dose of 1000 micrograms/day. @entity1 were randomly assigned inhaled placebo or inhaled @entity6410 24 micrograms bid for 4 weeks each in a crossover study. Bronchodilator dose-response curves were made at the end of each treatment period by use of cumulative doses of @entity6410 (6-108 micrograms) with FEV1 and FEF25-75 measured 30 min after each dose, and up to 6 h after the last dose. We calculated the degree of bronchodilator desensitisation by comparing the dose-response (for maximum and 6 h) after placebo with that after @entity6410 , and expressed this degree as a percentage of placebo response. @entity1 were divided into groups according to genotype at codon 16: homozygous @entity534 16 (n = 4), heterozygous @entity534 16/ @entity4022 16 (n = 8), and homozygous @entity4022 16 (n = 10). At codon 27: homozygous @entity7647 27 (n = 5), heterozygous @entity7647 27/ @entity367 27 (n = 11), and homozygous @entity367 27 (n = 6). FINDINGS: We found a significantly (p < 0.05) greater degree of bronchodilator desensitisation with homozygous @entity4022 16 than with homozygous @entity534 16 for maximal FEV1 response: -8% ( @entity534 16) vs 46% ( @entity4022 16); and for maximal FEF25-75 response: -32% ( @entity534 16) vs 74% ( @entity4022 16; 95% CI 15-92% and 49-164%, respectively). Bronchodilator responses at 6 h were also significantly (p < 0.05) different for FEV1 and FEF25-75 when @entity534 16 and @entity4022 16 were compared and values for heterozygous @entity534 16/ @entity4022 16 were intermediate. There was significantly greater desensitisation with @entity367 27 than with @entity7647 27 for maximal FEF25-75 response: -7% ( @entity7647 27) vs 68% ( @entity367 27), p = 0.05; and for 6 h FEF25-75 response: 43% ( @entity7647 27) vs 93% ( @entity367 27), p < 0.05 (95% CI 2-147% and 5-94%, respectively). All @entity1 who were homozygous @entity367 27 were also homozygous @entity4022 16. INTERPRETATION: We have found preliminary evidence that @entity2162 polymorphism is associated with altered @entity2162 expression in @entity565 @entity1 . The homozygous @entity4022 -16 form was significantly more prone to bronchodilator desensitisation than @entity534 16, with the influence of @entity4022 16 dominating over any putative protective effects of @entity367 27.

Association between XXXX polymorphism and susceptibility to bronchodilator desensitisation in moderately severe stable asthmatics.

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity2162 :: ('154', 'Gene') :: ['beta 2-AR', 'beta 2-adrenoceptor'] @entity565 :: ('MESH:D001249', 'Disease') :: ['asthma'] @entity4022 :: ('MESH:C066286', 'Chemical') :: ['Gly'] @entity534 :: ('CHEBI:16467', 'Chemical') :: ['Arg'] @entity7647 :: ('CHEBI:32668', 'Chemical') :: ['Gln'] @entity367 :: ('CHEBI:18237', 'Chemical') :: ['Glu'] @entity2263 :: ('10242', 'Gene') :: ['beta 2'] @entity6410 :: ('MESH:C012629', 'Chemical') :: ['formoterol']
@entity2162 :: (154,Gene) :: ['beta 2-adrenoceptor']
