Related Experiment Videos
Beta2-adrenergic receptor genetic polymorphisms and short-term bronchodilator responses in patients with COPD
Nobuyuki Hizawa1, Hironi Makita, Yasuyuki Nasuhara
1Department of Pulmonary Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Background:
COPD is characterized by a persistent airflow limitation that is not fully reversible; thus, the reversibility of airflow limitations in response to a bronchodilator is an important component of COPD. Several studies have established that two common nonsynonymous polymorphisms in the beta2-adrenergic receptor gene (ADRB2), Arg16Gly and Gln27Glu, have important effects in modulating responses to beta2-agonists; however, the effects of these polymorphisms on responses to beta2-agonists in patients with COPD is unknown.
Objective:
To examine whether different genotypes at these two polymorphisms are related to differential responses to inhaled beta2-agonists in patients with COPD.
Design And Participants:
A total of 246 patients with COPD who were participants in a longitudinal study of COPD (ie, the Hokkaido COPD cohort study) were studied. We compared short-term bronchodilator responses (BDRs) to salbutamol according to ADRB2 genotypes at codons 16 and 27.
Results:
The presence of the Arg16 allele was associated with lower BDRs to beta2-agonist inhalation. The mean (+/-SD) log (postbronchodilator FEV1-prebronchodilator FEV1) values of Gly16 homozygotes (n=65), Arg16Gly16 heterozygotes (n=106), and Arg16 homozygotes (n=75) were 2.19+/-0.43, 2.09+/-0.42, and 2.01+/-0.42, respectively (p<0.05). The genetic effects of the Arg16Gly polymorphism were independent of the severity of airflow limitation, age, and smoking status. The most common Arg16-Gln27 haplotype was also significantly associated with decreased BDRs to salbutamol (p<0.01).
Conclusion:
The genetic effects of ADRB2 gene polymorphisms may explain some of the variability in response to therapeutic doses of a short-acting beta2-agonists in patients with COPD.
Related Concept Videos
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Antiasthma Drugs: β2-Adrenoceptor Agonists
One class of bronchodilators includes β2-adrenoceptor agonists. These agents target the β2-adrenoceptors located on bronchial smooth muscle cells. By stimulating these receptors, β2-agonists induce relaxation in these...
Adrenergic Receptors: β Subtype
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors have equal affinities for...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features
Adrenergic Receptors (Adrenoceptors): Classification
α-Adrenoceptors
α-Adrenoceptors are classified into two main subtypes: α1 and α2. The α1 adrenoceptors, which are found on postsynaptic...