Taylor D Robin, Epton Michael J, Kennedy Martin A, Smith Andrew D, Iles Steven, Miller Allison L, Littlejohn Matthew D, Cowan Jan O, Hewitt Tracey, Swanney Maureen P, Brassett Karen P, Herbison G Peter
Otago Respiratory Research Unit and Department of Preventive and Social Medicine, Dunedin School of Medicine, New Zealand.
Am J Respir Crit Care Med. 2005 Sep 15;172(6):700-3. doi: 10.1164/rccm.200501-092OC. Epub 2005 Jun 23.
Genetic variation of the beta2-adrenoceptor (ADRB2) influences receptor function in vitro. There are reports that, in vivo, bronchodilator response is related to ADRB2 genotype, and that clinical outcomes during chronic therapy with beta2-agonist drugs are also influenced by genotype. Whether these features are related to single nucleotide polymorphisms or to combinations (haplotypes) is unclear.
Our aim was to measure bronchodilator response in patients with asthma stratified by ADRB2 haplotype. This was done after eliminating the confounding effect of prior drug treatment with inhaled beta2-agonists and corticosteroids.
ADRB2 haplotype was determined in 176 patients with asthma, of whom 161 harbored the six most common combinations. Treatment with inhaled beta2-agonists and inhaled corticosteroids was withheld for appropriate intervals. Spirometric changes 20 minutes after a single dose of albuterol (2.5 mg by nebulizer) were then recorded.
There were no significant differences in bronchodilator response (% improvement in FEV(1)) with respect to any of the major ADRB2 haplotypes or genotypes.
Genetic variation of the ADRB2 does not influence the immediate response to inhaled beta2-agonist. The confounding effect of tolerance resulting from regular beta2-agonist use must be controlled when assessing the pharmacogenetic influences on clinical outcomes with beta2-agonists.
β2肾上腺素能受体（ADRB2）的基因变异在体外会影响受体功能。有报道称，在体内，支气管扩张剂反应与ADRB2基因型有关，并且β2激动剂药物长期治疗期间的临床结局也受基因型影响。这些特征是与单核苷酸多态性还是与组合（单倍型）有关尚不清楚。
我们的目的是测定按ADRB2单倍型分层的哮喘患者的支气管扩张剂反应。这是在消除吸入性β2激动剂和皮质类固醇先前药物治疗的混杂效应后进行的。
测定了176例哮喘患者的ADRB2单倍型，其中161例具有六种最常见的组合。在适当的时间段内停用吸入性β2激动剂和吸入性皮质类固醇。然后记录单次剂量沙丁胺醇（通过雾化器给予2.5 mg）20分钟后的肺量计变化。
就任何主要的ADRB2单倍型或基因型而言，支气管扩张剂反应（FEV(1)改善百分比）均无显著差异。
ADRB2的基因变异不影响对吸入性β2激动剂的即时反应。在评估β2激动剂对临床结局的药物遗传学影响时，必须控制因定期使用β2激动剂导致的耐受性混杂效应。
