β2-Adrenergic Receptor Haplotype may be Associated with Susceptibility to Desensitization to Long-Acting β2-Agonists in COPD Patients

Abstract

Τhat β2-adrenergic receptor (β2AR) haplotypes may play a key role in clinical response to β2-agonists and haplotype Cys-19Gly16Gln27 (CysGlyGln) is reported to be associated with desensitization of β2AR to β-agonists in lymphocytes isolated from patients with asthma and septic shock. We sought to determine whether haplotypic variation of the β2AR affects the functional outcomes of long-acting β2-agonist (LABA) treatment for chronic obstructive pulmonary disease (COPD) when used as monotherapy. Treatment-naïve patients with COPD (n = 36) were prospectively treated with two kinds of LABA--inhaled salmeterol and transdermal tulobuterol patch--for 12 weeks in crossover study, and changes in pulmonary function data and 6-minute walk distance (6 MWD) were compared between groups stratified by the CysGlyGln. Frequencies of haplotype and diplotype for the CysGlyGln were 0.51 and 0.36, respectively. The individuals homozygous for CysGlyGln showed less improvement in FEV(1), %FEF(25-75 %), and IC/TLC than those with 0 or 1 copy of CysGlyGln after treatment with both LABAs despite initial bronchodilator responses to albuterol being similar in these groups. The response in these parameters was not significantly different between two types of LABA. Overall changes in 6 MWD in individuals with 2 copies of CysGlyGln versus 0 or 1 copy for salmeterol were 2.8 and 11 m, and for tulobuterol were -1.3 and 16 m, respectively. Homozygous haplotype for the CysGlyGln of β2AR may be associated with susceptibility to desensitization to LABA in patients with COPD.