Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Tsurumi-ku, Yokohama, Japan.
Department of Social Medicine, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan.
Br J Clin Pharmacol. 2021 Apr;87(4):1708-1716. doi: 10.1111/bcp.14570. Epub 2020 Oct 25.
The associations of 2 nonsynonymous single nucleotide polymorphisms (Arg16Gly and Gln27Glu) in the adrenoceptor β2 (ADRB2) gene with response after albuterol use are conflicting. We conducted a meta-analysis to examine the cumulative evidence of the effects of these 2 variants on percent forced expiratory volume in 1 second (FEV1.0%) after albuterol use in asthma patients.
We conducted a comprehensive literature search using MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify studies examining the association between ADRB2 Arg16Gly and Gln27Glu and FEV1.0% shortly after albuterol administration. The individual study results were combined with weights based on the inverse variance method. This systematic review was registered in the PROSPERO (registration number: CRD42019074554).
Among 273 initial studies identified, 7 studies met the inclusion criteria for quantitative evaluation. Results of the overall meta-analysis indicated no statistically significant mean difference of FEV1.0% between genotypes of Arg16Gly and Gln27Glu. In subgroup analyses, significant associations were found for Arg16Gly GG (vs AA) among studies where no methacholine bronchoconstriction was conducted (mean difference, -3.92; 95% confidence interval, -7.29 to -0.54; I = 0%), and for Arg16Gly GG (vs GA) among studies that included patients with no comorbidities (mean difference, -1.93; 95% confidence interval, -3.77 to -0.10; I = 0%).
Synthesis of the studies to date shows weak evidence for an association between ADRB2 Arg16Gly and Gln27Glu and FEV1.0% after albuterol use, results of which underscore significant heterogeneity across studies and the need for careful design and sample size considerations.
肾上腺素能受体β2(ADRB2)基因中的 2 个非同义单核苷酸多态性(Arg16Gly 和 Gln27Glu)与使用沙丁胺醇后的反应相关,但其关联结果存在冲突。我们进行了一项荟萃分析,以检查这些 2 种变体对哮喘患者使用沙丁胺醇后 1 秒用力呼气量(FEV1.0%)的累积证据。
我们使用 MEDLINE、EMBASE 和 Cochrane 对照试验中心注册库进行了全面的文献检索,以确定研究 ADREB2 Arg16Gly 和 Gln27Glu 与沙丁胺醇使用后 FEV1.0%之间关联的研究。个体研究结果与基于逆方差法的权重相结合。本系统评价已在 PROSPERO(注册号:CRD42019074554)中注册。
在最初确定的 273 项研究中,有 7 项研究符合定量评估的纳入标准。总体荟萃分析结果表明,Arg16Gly 和 Gln27Glu 基因型之间的 FEV1.0% 无统计学显著差异。在亚组分析中,在未进行乙酰甲胆碱支气管收缩的研究中,Arg16Gly GG(与 AA)基因型之间存在显著关联(平均差异,-3.92;95%置信区间,-7.29 至-0.54;I = 0%),在包括无合并症患者的研究中,Arg16Gly GG(与 GA)基因型之间存在显著关联(平均差异,-1.93;95%置信区间,-3.77 至-0.10;I = 0%)。
迄今为止的研究综合表明,ADRB2 Arg16Gly 和 Gln27Glu 与使用沙丁胺醇后的 FEV1.0%之间存在关联的证据较弱,结果表明研究之间存在显著异质性,需要仔细设计和考虑样本量。