The Lancet：哮喘药物疗效与患者基因型无关
2008年1月4日的爱思唯尔期刊《柳叶刀》（The Lancet）刊登了一项关于对常用治疗哮喘的药物长效型β受体激动剂的研究。研究结果表明，该药物的治疗效果可能与患者的基因型（基因变异）无关。
哮喘病是仅次于艾滋病、肿瘤、心脑血管病等严重危害人类生存质量的第四大杀手。在美国大约有10％的人受到哮喘病的困扰，每年约有4000人直接死于哮喘病。大多数学者认为哮喘是一种具有多基因遗传倾向的疾病。在1993年首次确定了β2肾上腺素能受体（ADRB2）所有的变异，此后这一基因与哮喘的关系就成为哮喘研究的一大热点。之前研究认为携有β肾上腺素能受体（ADRB2）基因型患者其对治疗哮喘病的常用药物——长效β受体激动剂药效有很大的影响。
在最新的研究中，科学家对携有ADRB2基因变异的哮喘病患者接受长效β受体激动剂结合使用吸入性类固醇药物治疗进行了临床试验。接受试验的患者都会随机接受一到两种不同的长效型β激动剂的治疗。结果表明，患者哮喘症状都有所改善，但并未观察到携有(ADRB2)基因型患者在对用药治疗上有任何差异。同时，研究人员建议患者使用综合疗法，即长效β受体激动剂结合吸入性类固醇，以控制中度和重度持续性哮喘。（科学网 于乃森/编译）
（《柳叶刀》（The Lancet），doi:10.1016/S0140-6736(07)61906-0，Eugene R Bleecker, Mitch Goldman）
生物谷推荐原始出处：
The Lancet
Volume 370, Issue 9605, 22 December 2007-4 January 2008, Pages 2118-2125
Effect of ADRB2 polymorphisms on response to longacting β2-agonist therapy: a pharmacogenetic analysis of two randomised studies
Prof Eugene R Bleecker MDa, 
, 
, Prof Dirkje S Postma MDb, Rachael M Lawrance BScd, Prof Deborah A Meyers PhDa, Helen J Ambrose PhDc and Mitch Goldman MDd
aCenter for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA
bDepartment of Pulmonology, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
cAstraZeneca, Macclesfield, UK
dAstraZeneca, Wilmington, DE, USA
Summary
Background
New evidence has suggested that people with asthma who are homozygous for arginine at aminoacid 16 of the β2-adrenergic receptor (ADRB2) might not benefit from longacting β2-agonist therapy. We, therefore, investigated whether ADRB2 polymorphisms affect response to longacting β2-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 β2-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 β2-agonists
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