β_2-AR多态性对COPD患者支气管舒张反应的影响

Effect of β-AR genetic polymorphism on bronchodilator response in COPD patients

目的 探讨 β2 -肾上腺素能受体 (β2 - AR)编码区 16位点基因多态性对慢性阻塞性肺病 (COPD)支气管舒张反应的影响。方法 用直接测序法确定 34例 COPD患者的基因型 ,其中野生型组 (Arg16 Arg) 16例、突变型组 (Arg16 Gly+Gly16 Gly) 18例 ;以 1秒钟用力呼气量 (FEV1 )占预计值 %为指标 ,分别吸入沙丁胺醇、溴化异丙托品及两药联合 ,观察药物吸入前及吸入后 15、30、6 0、12 0、180、36 0分钟 FEV1 占预计值 %的变化 ,分析基因多态性对支气管舒张反应的影响。结果 吸入沙丁胺醇后 ,野生型组 FEV1 占预计值 %平均改善率及最大改善率都强于突变型组 ,差异有显著性 (P均 <0 .0 5 ) ;突变型组吸入溴化异丙托品后的 FEV1 占预计值 %平均改善率高于吸入沙丁胺醇后 ,差异有显著性 (P<0 .0 5 ) ;两药联合吸入时患者 FEV1 占预计值 %平均改善率分别强于吸入沙丁胺醇和溴化异丙托品后 (P均 <0 .0 5 )。结论 β2 - AR16位点多态性是影响 COPD吸入沙丁胺醇、溴化异丙托品后支气管舒张反应性的重要原因之一。

Objective To investigate t he impact of genetic polymorphisms of β 2-adrenergic receptor(β 2-AR) in 16 position on bronchodilator response i n COPDs.Methods 34 COPD patients were genotyped by se quencing,and divided into wild-type gr oup (Arg16Arg)and mutant-type group(Arg16Gly+Gly16Gly).Each g roup received inhaled albuterol,inhaled atrovent or inhaled atrovent plus albut erol.Lung funtion (FEV 1% pre) was assessed before drug administration and 15,30,60,120,180,360 minutes t herafter.Effects of genetic polymorphisms on bronchodilator re sponse were further analyzed.Results After administrat ion of inhaled albuterol,in wild-type g roup,average percentage increase and maximal percentage increase in FEV 1 %pre significantly improved compared with in mutant-type group(P< 0.05) .In mutant-type group,after administration of inhaled atrovent,average perce ntage increase in FEV 1 %pre significantly improved compared with i nhaled albuterol(P<0.05).Combination trea tment with albuterol plus atrovent provided significantly( P<0.05) greater improvements in average percentage in crease in FE V 1% pre than those given alone.Conclusions β 2-AR genetic polymorphism in 16 position is a major determinant of bronchodilator response to albuterol and atrovent in COPDs.