The effect of polymorphisms of the β2-adrenergic receptor on the response to regular use of albuterol in asthma
The effect of polymorphisms of the β2-adrenergic receptor on the response to regular use of albuterol in asthma
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DOI：
10.1164/ajrccm.162.1.9907092
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发表时间：
2000-07-01
影响因子：
24.7
通讯作者：
Yandava, CN
中科院分区：
文献类型：
--
作者：
Israel, E;Drazen, JM;Yandava, CN
吸入性β-肾上腺素能受体激动剂是治疗哮喘最常用的药物，尽管有证据表明经常使用可能会对某些患者产生不良反应。β（2）-肾上腺素能受体（β（2）-AR）的多态性可影响受体的调节。较小的研究检查这种多态性对p-激动剂治疗反应的影响，产生了不一致的结果。我们通过对190名哮喘患者进行基因分型，研究β 2-AR的密码子16（β 2-AR-16）和密码子27（β 2-AR-27）多态性是否可能影响对定期与按需使用沙丁胺醇的反应，这些患者参加了一项研究定期与按需使用沙丁胺醇效果的试验。在16周的治疗期间，定期使用沙丁胺醇的B-2-AR-16（Arg/Arg）精氨酸纯合子患者的早晨呼气峰流速略有下降。在4周的运行期内，这种效应被放大，在此期间，所有患者都恢复使用按需沙丁胺醇，因此，到研究结束时，定期使用沙丁胺醇的Arg Arg患者的早晨呼气峰流速比按需使用沙丁胺醇的Arg/Arg患者低30.5 +/- 12.1 L/min（p = 0.012）。在β（2）-AR-16甘氨酸纯合子患者中，定期使用沙丁胺醇未导致峰值血流下降。在定期使用沙丁胺醇的Arg/Arg患者中，夜间呼气峰流量也下降，但在按需使用沙丁胺醇的患者中没有下降。常规治疗和按需治疗的结果无显著差异，与β 2-AR第27位多态性相关。我们所研究的哮喘预后与这些β 2-AR多态性之间没有其他差异。β（2）-AR的多态性可能影响气道对常规吸入β-激动剂治疗的反应。
Inhaled P-adrenergic agonists are the most commonly used medications for the treatment of asthma although there is evidence that regular use may produce adverse effects in some patients. Polymorphisms of the beta(2)-adrenergic receptor (beta(2)-AR) can affect regulation of the receptor. Smaller studies examining the effects of such polymorphisms on the response to p-agonist therapy have produced inconsistent results. We examined whether polymorphisms at codon 16 (beta(2)-AR-16) and codon 27 (beta(2)-AR-27) of the beta(2)-AR might affect the response to regular versus as-needed use of albuterol by genotyping the 190 asthmatics who had participated in a trial examining the effects of regular versus as needed albuterol use. During the 16-wk treatment period there was a small decline in morning peak expiratory flow in patients homozygous for arginine at B-2-AR-16 (Arg/Arg) who used albuterol regularly. This effect was magnified during a 4-wk run out period, during which all patients returned to using as-needed albuterol, so that by the end of the study Arg Arg patients who had regularly used albuterol had a morning peak expiratory flow 30.5 +/- 12.1 L/min lower (p = 0.012) than Arg/Arg patients who had used albuterol on an as needed basis. There was no decline in peak flow with regular use of albuterol in patients who were homozygous for glycine at beta(2)-AR-16. Evening peak expiratory flow also declined in the Arg/Arg patients who used albuterol regularly but not in those who used albuterol on an as-needed basis. No significant differences in outcomes between regular and as-needed treatment were associated with polymorphisms at position 27 of the beta(2)-AR. No other differences in asthma outcomes that we investigated occurred in relation to these beta(2)-AR polymorphisms. Polymorphisms of the beta(2)-AR may influence airway responses to regular inhaled p-agonist treatment.