Gly16Arg ADRB2基因多态性对日本轻度持续性哮喘患者沙美特罗或孟鲁司特反应的影响。

The effects of a Gly16Arg ADRB2 polymorphism on responses to salmeterol or montelukast in Japanese patients with mild persistent asthma.

作者信息

Konno Satoshi, Hizawa Nobuyuki, Makita Hironi, Shimizu Kaoruko, Sakamoto Tohru, Kokubu Fumio, Saito Takefumi, Endo Takeo, Ninomiya Hiroki, Iijima Hiroaki, Kaneko Norihiro, Ito Yoichi M, Nishimura Masaharu

机构信息

aFirst Department of Medicine, Hokkaido University School of Medicine, Sapporo bDepartment of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba cDepartment of Respiratory Medicine, Showa University Fujigaoka Hospital, Tokyo dDepartment of Respiratory Medicine, Ibaraki Higashi National Hospital, Ibaraki eDepartment of Respiratory Medicine, Mito Medical Center, Mito fDepartment of Respiratory Medicine, Kobari General Hospital, Chiba gDepartment of Respiratory Medicine, Tsukuba Medical Center, Tsukuba hDepartment of Respiratory Medicine, Kameda Medical Center, Chiba iDepartment of Biostatistics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

出版信息

Pharmacogenet Genomics. 2014 May;24(5):246-55. doi: 10.1097/FPC.0000000000000043.

DOI:10.1097/FPC.0000000000000043

PMID:24681963

Abstract

BACKGROUND

Long-acting β2-agonists and leukotriene receptor antagonists are two principal agents that can be added to inhaled corticosteroids (ICS) for patients with asthma that is not adequately controlled by ICS alone. The Gly16Arg genotype of the β2-adrenergic receptor (ADRB2) gene may influence the bronchodilator effects of β2-agonists. We hypothesized that differential responses to long-acting β2-agonists or leukotriene receptor antagonists might be determined partly by the Gly16Arg polymorphism in Japanese asthma patients.

MATERIALS AND METHODS

This randomized, genotype-stratified, two-period crossover study included 80 patients with mild-to-moderate asthma (35 Arg/Arg and 45 Gly/Gly individuals). The primary study outcome was the difference in peak expiratory flow (ΔPEF) (ΔPEF, l/min) by genotype after 16 weeks of treatment with salmeterol (ΔPEFsal) or montelukast (ΔPEFmon). In addition, multivariate analyses were used to identify independent factors that were predictive of responses to each treatment.

RESULTS

The mean ΔPEFsal-ΔPEFmon was 19.3±46.6 among Arg/Arg individuals and 16.8±51.5 among Gly/Gly individuals, indicating that the Gly16Arg genotype did not influence the differential bronchodilator effect of the two agents. Multivariate analysis showed that higher peripheral eosinophil counts were associated with better response to salmeterol (P<0.05).

CONCLUSION

The Gly16Arg genotype did not influence the differential bronchodilator effect of salmeterol or montelukast as an add-on therapy to ICS within 16 weeks of follow-up. Higher peripheral eosinophil counts may be associated with better responses to salmeterol in combination with ICS.

摘要

背景

长效β2受体激动剂和白三烯受体拮抗剂是两类主要药物，可添加到吸入性糖皮质激素（ICS）中，用于治疗单用ICS无法得到充分控制的哮喘患者。β2肾上腺素能受体（ADRB2）基因的Gly16Arg基因型可能会影响β2受体激动剂的支气管扩张作用。我们推测，日本哮喘患者对长效β2受体激动剂或白三烯受体拮抗剂的不同反应可能部分由Gly16Arg多态性决定。

材料与方法

这项随机、按基因型分层、两阶段交叉研究纳入了80例轻至中度哮喘患者（35例Arg/Arg个体和45例Gly/Gly个体）。主要研究结局是使用沙美特罗（ΔPEFsal）或孟鲁司特（ΔPEFmon）治疗16周后，按基因型分组的呼气峰值流速差异（ΔPEF）（ΔPEF，升/分钟）。此外，采用多变量分析来确定预测每种治疗反应的独立因素。