2008年1月4日的愛思唯爾期刊《柳葉刀》（The Lancet）刊登了一項關(guān)于對常用治療哮喘的藥物長效型β受體激動劑的研究,。研究結(jié)果表明,，該藥物的治療效果可能與患者的基因型（基因變異）無關(guān)。
哮喘病是僅次于艾滋病,、腫瘤,、心腦血管病等嚴重危害人類生存質(zhì)量的第四大殺手。在美國大約有10％的人受到哮喘病的困擾,，每年約有4000人直接死于哮喘病,。大多數(shù)學者認為哮喘是一種具有多基因遺傳傾向的疾病。在1993年首次確定了β2腎上腺素能受體（ADRB2）所有的變異,，此后這一基因與哮喘的關(guān)系就成為哮喘研究的一大熱點,。之前研究認為攜有β腎上腺素能受體（ADRB2）基因型患者其對治療哮喘病的常用藥物——長效β受體激動劑藥效有很大的影響。
在最新的研究中,，科學家對攜有ADRB2基因變異的哮喘病患者接受長效β受體激動劑結(jié)合使用吸入性類固醇藥物治療進行了臨床試驗,。接受試驗的患者都會隨機接受一到兩種不同的長效型β激動劑的治療。結(jié)果表明,，患者哮喘癥狀都有所改善,，但并未觀察到攜有(ADRB2)基因型患者在對用藥治療上有任何差異。同時,，研究人員建議患者使用綜合療法,，即長效β受體激動劑結(jié)合吸入性類固醇，以控制中度和重度持續(xù)性哮喘,。（科學網(wǎng) 于乃森/編譯）
（《柳葉刀》（The Lancet）,，doi:10.1016/S0140-6736(07)61906-0，Eugene R Bleecker, Mitch Goldman）
生物谷推薦原始出處：
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
