β_2-AR多态性对哮喘支气管舒张反应曲线的影响  

The Impact of Genetic Polymorphisms of β_2-adrenegic Receptor on Bronchodilator Response in Asthma

作　　者：戴路明[1] 张剑青[1] 赵之焕[1] 方利州[1] 张亚平[2] 王曾礼[3] 

机构地区：[1]昆明医学院第一附属医院呼吸内科,昆明650032 [2]中科院昆明动物研究所,昆明650051 [3]华西医科大学第一附属医院呼吸内科,成都610041

出　　处：《昆明医学院学报》2004年第1期9-13,共5页Journal of Kunming Medical College

基　　金：国家自然科学基金资助项目 (39770 340 )

摘　　要：目的 :探讨 β2 肾上腺素受体编码区 16 ,2 7位点基因突变对哮喘支气管舒张反应的影响 .方法 :通过测序确定 2 2名哮喘患者的基因突变类型 ,以FEV1为指标 ,观测吸入 4 0 0 μg沙丁胺醇后 7h支气管舒张反应性曲线 ,进一步分析基因突变对支气管舒张反应的影响 .结果 :2 2例基因型分别为 :16位点 (Arg/Arg8例 ;Arg/Gly 8例 ;Gly/Gly 6例 ) ;2 7位点 (Gln/Gln 17例 ;Gln/Glu 3例 ;Glu/Glu 2例 ) .2 2例哮喘的基础FEV1无显著性差异 ,但 16位点 3种基因型 (A组Arg/Arg ,B组Arg/Gly及C组Gly/Gly)对吸入 4 0 0 μg沙丁胺醇后支气管舒张反应性曲线的影响差异较大 :△FEV1峰值 %分别为 (19 2± 1 3) ,(12 6± 0 9)及(12 1± 0 9) ,A∶BP <0 0 0 1;A∶CP <0 0 0 1;出现时间为 15 ,6 0及 6 0min ;起始斜率为 4 4 0± 0 19,1 11± 0 0 5及 0 98± 0 0 4 ,A∶BP <0 0 5 ;A∶CP <0 0 5 ;曲线下面积 :4 2 2± 0 18,2 5 2± 0 11及 2 2 7±0 10 ,A∶BP <0 0 0 1;A∶CP <0 0 0 1.而 2 7位点各基因型对吸入沙丁胺醇后支气管舒张反应性曲线的影响无显著差异 .结论 :β2 肾上腺素受体Objective: To investigate the impact of genetic polymorphisms of β 2-adrenegic receptor (β 2-AR) in 16 and 27 positions on bronchodilator response in asthma. Methods: We genotyped 22 participants by sequencing, FEV 1 was determined at various times after administration of an inhaled 400?μg albuterol, and further the relationship between the bronchodilator response to albuterol and the gene mutation was analyzed. Results: The genotypes of 22 asthmas were 8 Arg/Arg, 8 Arg/Gly and 6 Gly/Gly in 16 position respectively; and 17 Gln/gln, 3 Gln/glu, 2 Glu/Glu in 27 position respectively. The baseline FEV 1 of 22 asthmas had no difference, but the genotypes Arg/Arg (A), Arg/Gly (B) and Gly/Gly (C) in 16 position had more different effect on albuterol-evoked FEV1: maximal percentage increased in FEV1 (△FEV 1%) (19.2±1.3, 12.6±0.9, A∶B P<0.001; A∶C P<0.001); the peak times for △FEV 1% respectively were 15?min and 60?min; initial slopes respectively were 4.40±0.19, 11±0.05 and 0.98±0.04, A∶B P<0.05; A∶C P<0.05. The areas under albuterol-evoked FEV 1 -time curve were 4.22±0.18, 2.25±0.11 and 2.27±0.10, A∶B P<0.001; A∶C P<0.001 respectively, whereas the genotypes in 27 position had similar effect on albuterol-evoked bronchodilator response. Conclusions: The β 2-adrenegic receptor gene polymorphism in 16 position is a major determinant of bronchodilator response to albuterol in asthmas.

关 键 词：β2—AR多态性 哮喘 支气管舒张反应曲线 遗传多态性 

分 类 号：R562.25[医药卫生—呼吸系统]