β2肾上腺素能受体基因多态性可预测急性哮喘患儿对β2激动剂的反应。

Beta2-adrenoceptor polymorphisms predict response to beta2-agonists in children with acute asthma.

作者信息

Martin Andrew C, Zhang Guicheng, Rueter Kristina, Khoo Siew-Kim, Bizzintino Joelene, Hayden Catherine M, Geelhoed Gary C, Goldblatt Jack, Laing Ingrid A, Le Souëf Peter N

机构信息

School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia.

出版信息

J Asthma. 2008 Jun;45(5):383-8. doi: 10.1080/02770900801971792.

DOI:10.1080/02770900801971792

PMID:18569231

Abstract

The aim of this study was to determine the influence of single nucleotide polymorphisms in the beta(2)-adrenoceptor gene, on the response to inhaled beta(2)-agonists in children with acute asthma. We hypothesised that children with polymorphisms that generate enhanced receptor downregulation in vitro, Gly16 and Gln27, would have a slower response to beta(2)-agonist therapy during acute asthma. One hundred and forty-eight children with acute asthma were recruited and genotyped for beta(2)Arg16Gly and beta(2)Gln27Glu. For Gln27Glu, individuals Gln27Gln took longest to stretch out to 1, 2 and 4 hourly beta(2)-agonists, followed by heterozygotes who were intermediate and Glu27Glu who responded most rapidly (1 hourly: 2.6 hr vs. 2.0 vs. 1.4, p = 0.02; 2 hourly: 10.6 hr vs. 10.7 vs. 6.8, p = 0.07; 4 hourly: 29.8 hr vs. 28.5 vs. 24.3, p = 0.30). The ability to prospectively identify children who respond less effectively to beta (2)-agonists during an acute asthma attack has the potential to allow the generation of genotype-specific treatment pathways.

摘要

本研究的目的是确定β₂肾上腺素能受体基因单核苷酸多态性对急性哮喘患儿吸入β₂激动剂反应的影响。我们假设，在体外产生增强受体下调的多态性儿童，即Gly16和Gln27，在急性哮喘期间对β₂激动剂治疗的反应会较慢。招募了148名急性哮喘患儿，并对其进行β₂Arg16Gly和β₂Gln27Glu基因分型。对于Gln27Glu，Gln27Gln个体对每小时1次、2次和4次β₂激动剂的舒张反应时间最长，其次是杂合子，其反应时间处于中间，而Glu27Glu个体反应最快（每小时1次：2.6小时对2.0小时对1.4小时，p = 0.02；每小时2次：10.6小时对10.7小时对6.8小时，p = 0.07；每小时4次：29.8小时对28.5小时对24.3小时，p = 0.30）。前瞻性识别在急性哮喘发作期间对β₂激动剂反应较差的儿童，有可能产生基因型特异性治疗途径。