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.


CONCLUSIONS
Gln27 polymorphism might be a marker for adverse clinical outcomes with chronic beta2-agonist exposure in children with asthma from Argentina.
Giubergia
Verónica
V
Pulmonology Department, Hospital de Pediatría Dr. Juan P. Garrahan, Buenos Aires, Argentina.
Gravina
Luis Pablo
LP
Castaños
Claudio
C
Chertkoff
Lilien
L
Grenoville
Mario
M
D000293:Adolescent; D000420:Albuterol / Q000627:therapeutic use*; D001118:Argentina; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002648:Child; D004361:Drug Tolerance / Q000235:genetics; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D013147:Spirometry; D013997:Time Factors
D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D000420:Albuterol