Giubergia Verónica, Gravina Luis Pablo, Castaños Claudio, Chertkoff Lilien, Grenoville Mario
Pulmonology Department, Hospital de Pediatría Dr. Juan P. Garrahan, Buenos Aires, Argentina.
Pediatr Pulmonol. 2008 May;43(5):421-5. doi: 10.1002/ppul.20759.
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).
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.
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.
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.
Gln27 polymorphism might be a marker for adverse clinical outcomes with chronic beta2-agonist exposure in children with asthma from Argentina.
多项研究表明，长期使用短效β2-肾上腺素能激动剂后，药物的支气管扩张作用可能会下降，这种情况可能与β2-肾上腺素能受体（β2-AR）的多态性有关。
评估阿根廷哮喘儿童中β2-AR多态性的频率，并评估其对4周沙丁胺醇治疗期间支气管扩张脱敏作用的影响。
测定了117名哮喘儿童的β2-AR基因型，其中101名儿童接受了4周的沙丁胺醇治疗。在研究开始时（第1天）和结束时（第30天）记录第一秒用力呼气容积（FEV(1)）的肺功能变化，并与受体第16和27位的基因型进行比较。计算了所有人群中多态性的频率。
在该阿根廷研究人群中，第27位谷氨酰胺（Gln27）的出现频率明显高于其他白种人群。Gln27多态性的纯合性与受体脱敏有关，长期使用后对沙丁胺醇的支气管扩张反应下降。
Gln27多态性可能是阿根廷哮喘儿童长期接触β2-激动剂后不良临床结局的一个标志物。
