ADRB多态性与长效β2受体激动剂的疗效:对两个随机对照试验进行的药物基因学分析
2008/06/06
有证据表明β2受体第16位氨基酸为精氨酸纯合子的哮喘患者应用长效β2受体激动剂的疗效差。 作者按照ADRB基因型分组统计了两项随机对照试验纳入的哮喘患者，观察吸入激素联合长效β2受体激动剂治疗对哮喘急性加重的影响。在第一项研究为双盲研究，2250名哮喘患者随机分为三组，分别给予布地奈德联合福莫特罗用作维持和缓解治疗，固定剂量的布地奈德联合福莫特罗或固定剂量的氟替卡松联合沙美特罗治疗，治疗时间为6个月。第二项研究为开放研究，纳入405名哮喘患者，分为调整剂量布地奈德联合福莫特罗组，固定剂量布地奈德联合福莫特罗组和固定剂量氟替卡松联合沙美特罗组，治疗时间为7个月。作者分别分析了ADRB多态性与哮喘严重急性发作和其他终点指标的关系。两个研究的主要的终点指标分别为哮喘严重急性发作和根据急性发作次数评价的哮喘控制水平。
结果表明研究1中Gly16Arg基因型对整个治疗组中严重急性加重患者的百分比无影响（833名Gly/Gly者中有99名[12%]发生急性加重，1028名Gly/Arg者中有110名[11%]发生急性加重,361名Arg/Arg者中有32名[9%]发生急性加重。次要终点指标包括1秒呼出气量，峰流速，急救用药次数，夜间觉醒次数各基因型组之间均无显著差异。ADRB2 基因型和主要及次要终点指标之间均无相关。在第2项研究中，各个ADRB2基因组哮喘急性加重的次数和其他研究终点指标都很相似。
作者认为ADRB基因型对哮喘患者的治疗反应并无影响，不管何种基因型均可继续应用吸入激素和长效β2受体激动剂联合治疗。
（马艳良 北京大学人民医院呼吸科 100044 摘译）
(Lancet. 2007 Dec 22;370(9605):2118-2125)
Effect of ADRB2 polymorphisms on response to longacting beta2-agonist therapy: a pharmacogenetic analysis of two randomised studies.Bleecker ER, Postma DS, Lawrance RM, Meyers DA, Ambrose HJ, Goldman M.
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA. ebleeck@wfubmc.edu
BACKGROUND: New evidence has suggested that people with asthma who are homozygous for arginine at aminoacid 16 of the beta2-adrenergic receptor (ADRB2) might not benefit from longacting beta2-agonist therapy. We, therefore, investigated whether ADRB2 polymorphisms affect response to longacting beta2-agonists in combination with inhaled corticosteroids.
METHODS: Asthmatics were stratified by ADRB2 genotype in two studies to assess the effects of inhaled corticosteroids plus longacting beta2-agonists on asthma exacerbations. In study 1 (double-blind), 2250 asthmatics were randomly assigned to budesonide plus formoterol maintenance and reliever therapy, fixed-dose budesonide plus formoterol, or fixed-dose fluticasone plus salmeterol for 6 months. Study 2 (open-label) consisted of 405 asthmatics and compared an adjustable regimen of budesonide plus formoterol with fixed-dose budesonide plus formoterol and fixed-dose fluticasone plus salmeterol for 7 months. The relation between ADRB2 polymorphism, severe asthma exacerbations, and other asthma outcomes was analysed. Primary endpoints for studies 1 and 2 were severe asthma exacerbation and asthma control as assessed by measures of exacerbations, respectively.
FINDINGS: In study 1, Gly16Arg genotype had no effect on the percentage of participants with severe exacerbations across all treatment groups (99 [12%] of 833 Gly/Gly, 110 [11%] of 1028 Gly/Arg, and 32 [9%] of 361 Arg/Arg participants). Secondary endpoints, including forced expiratory volume in 1 s, peak expiratory flow, use of as-needed medication, and number of nights with awakenings were similar between genotype groups. No relation was recorded between ADRB2 haplotype and primary and secondary endpoints. In study 2, the frequency of asthma exacerbations (15 [9%] of 168 Gly/Gly, 13 [8%] of 169 Gly/Arg, and 6 [9%] of 67 Arg/Arg participants) and other study endpoints were closely similar for all ADRB2 genotypes.
INTERPRETATION: Since we showed no pharmacogenetic effect of ADRB2 variation on therapeutic response in asthma, patients, irrespective of their genotype, can continue to receive inhaled corticosteroids plus longacting beta2-agonists.
上一篇：
可溶性TNF-α受体融合蛋白(Etanercept)对激素抵抗的难治性哮喘的作用：一项双盲、随机、安
下一篇：
重组人脱氧核糖核酸酶对小儿急性哮喘的治疗效果
