Influence of beta2-adrenoceptor polymorphisms on the response to chronic use of albuterol in asthmatic children.

BACKGROUND: Several studies have suggested that after regular use of short acting beta2-agonists the bronchodilator effect of the drug may decline and this condition would be related to polymorphisms of the beta2-adrenergic receptor (beta2-AR).

OBJECTIVE: To assess the frequency of beta2-AR polymorphisms in asthmatic children from Argentina, and to evaluate their influence on bronchodilator desensitization to albuterol over a 4-week treatment.

METHODS: beta2-AR genotypes were determined in 117 children with asthma and 101 of them were under 4 weeks treatment with albuterol. Spirometric changes in FEV(1) were recorded at the beginning (day 1) and at the end of the study (day 30) and compared to genotypes at position 16 and 27 of the receptor. The frequency of the polymorphisms was calculated in all population.

RESULTS: The presence of glutamine at position 27 (Gln27) was significantly more frequent in this Argentinean study population than in other Caucasian populations. The homozygosity for Gln27 polymorphism was associated to a desensitization of the receptor with a decline in the bronchodilator response to albuterol after chronic use.

CONCLUSION: Gln27 polymorphism might be a marker for adverse clinical outcomes with chronic beta2-agonist exposure in children with asthma from Argentina.