Beta2-adrenergic receptor haplotype and bronchodilator response to salbutamol in patients with acute exacerbations of COPD
Michal Mokry, Pavol Joppa, Eva Slaba, Jozef Zidzik, Viera Habalova, Zuzana Kluchova, Lydia Micietova, Eva Rozborilova, Jan Salagovic, Ruzena Tkacova
Med Sci Monit 2008; 14(8): CR392-398
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 and Method: 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.
Keywords: Receptors, Adrenergic, beta-2 - genetics, Pulmonary Disease, Chronic Obstructive - physiopathology, Haplotypes, Glycine - genetics, Glutamic Acid - genetics, Demography, Respiratory Function Tests, Codon - genetics, Bronchodilator Agents - therapeutic use, Albuterol - therapeutic use, Adult