慢性阻塞性肺疾病急性加重患者的β2肾上腺素能受体单倍型与沙丁胺醇的支气管扩张反应

Beta2-adrenergic receptor haplotype and bronchodilator response to salbutamol in patients with acute exacerbations of COPD.

作者信息

Mokry Michal, Joppa Pavol, Slaba Eva, Zidzik Jozef, Habalova Viera, Kluchova Zuzana, Micietova Lydia, Rozborilova Eva, Salagovic Jan, Tkacova Ruzena

机构信息

Department of Respiratory Medicine, Faculty of Medicine and L. Pasteur Teaching Hospital, Kosice, Slovakia.

出版信息

Med Sci Monit. 2008 Aug;14(8):CR392-8.

PMID:18667995

Abstract

BACKGROUND

The role of the beta2-adrenergic receptor (ADRB2) genotype in patients with chronic obstructive pulmonary disease (COPD) is unclear. In patients with acute exacerbations of COPD (AECOPD), we assessed the role of ADRB2 haplotypes in morning lung function and in the bronchodilator response to salbutamol.

MATERIAL/METHODS: In 107 patients with AECOPD, polymorphisms in the amino acid position 16 (Arg16/Gly16) and 27 (Gln27/Glu27) of the ADRB2 gene were assessed by allele-specific polymerase chain reaction, identifying 31 subjects with the Gly16/Glu27-negative and 76 with the Gly16/Glu27-positive ADRB2 haplotype. Pulmonary function and bronchodilator response to salbutamol were assessed using bodyplethysmography.

RESULTS

Forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) were significantly higher in the Gly16/Glu27-negative compared to the Gly16/Glu27-positive haplotype group at baseline (49.7+/-2.9% vs 42.4+/-1.8% predicted, P=0.037; 44.0+/-2.2% vs 36.4+/-1.6% predicted, P=0.008, respectively). FEV1, PEF, and forced vital capacity (FVC) increased from baseline to after salbutamol treatment in both the Gly16/Glu27-negative and the Gly16/Glu27-positive ADRB2 haplotype groups (P<0.001 for all comparisons). Values for FEV1 and PEF after administration of the bronchodilator were significantly higher in the Gly16/Glu27-negative haplotype group compared with the Gly16/Glu27-positive haplotype group (P=0.030 and P=0.034, respectively). No differences were observed in DeltaFEV1, DeltaPEF, or DeltaFVC after bronchodilation between the 2 ADRB2 haplotype groups (12.2+/-1.8% vs 14.5+/-1.5% predicted, P=0.393; 12.2+/-3.3% vs 20.8+/-3.2% predicted, P=0.117; 9.1+/-2.3% vs 10.4+/-1.9% predicted, P=0.707, respectively).

CONCLUSIONS

The present findings suggest that the ADBR2 gene haplotypes may affect the severity of obstructive ventilatory impairment but not the immediate response to salbutamol during AECOPD.

摘要

背景

β2-肾上腺素能受体（ADRB2）基因型在慢性阻塞性肺疾病（COPD）患者中的作用尚不清楚。在慢性阻塞性肺疾病急性加重期（AECOPD）患者中，我们评估了ADRB2单倍型在晨肺功能及沙丁胺醇支气管舒张反应中的作用。

材料/方法：对107例AECOPD患者，采用等位基因特异性聚合酶链反应评估ADRB2基因第16位氨基酸（Arg16/Gly16）和第27位氨基酸（Gln27/Glu27）的多态性，确定31例Gly16/Glu27阴性和76例Gly16/Glu27阳性ADRB2单倍型患者。采用体描法评估肺功能及沙丁胺醇支气管舒张反应。

结果

基线时，Gly16/Glu27阴性单倍型组的1秒用力呼气容积（FEV1）和呼气峰值流速（PEF）显著高于Gly16/Glu27阳性单倍型组（预计值分别为49.7±2.9% 对42.4±1.8%，P = 0.037；44.0±2.2% 对36.4±1.6%，P = 0.008）。Gly16/Glu27阴性和Gly16/Glu27阳性ADRB2单倍型组的FEV1、PEF和用力肺活量（FVC）从基线至沙丁胺醇治疗后均增加（所有比较P<0.001）。支气管舒张剂给药后，Gly16/Glu27阴性单倍型组的FEV1和PEF值显著高于Gly16/Glu27阳性单倍型组（分别为P = 0.030和P = 0.034）。两组ADRB2单倍型支气管舒张后在FEV1、PEF或FVC变化值方面未观察到差异（预计值分别为12.2±1.8% 对14.5±1.5%，P = 0.393；12.2±3.3% 对20.8±3.2%，P = 0.117；9.1±2.3% 对10.4±1.9%，P = 0.707）。