Polymorphism of Beta2-Adrenoceptor and Regular Use of Formoterol in Asthma: Preliminary Results

Abstract

Polymorphism at codon 16 of the beta2-adrenoceptor (beta2-AR) affects the responsiveness to salmeterol in asthmatics. Data concerning formoterol are more controversial in the literature. The aim of this study was to verify whether homozygous for arginine-16 (ArgArg16) and homozygous for glycine-16 (GlyGly16) genotypes differently influence the long-term responsiveness to formoterol. Twenty-nine patients with mild-to-moderate asthma, in stable clinical conditions, underwent genotyping at codon 16 of the beta2-AR by RFLP-PCR assay. The effects of a 4-week monotherapy with formoterol (12 g BID) were tested on the peak expiratory flow (PEF) variability and the forced expiratory volume in 1 sec (FEV1) slope of the dose-response curve to salbutamol. Variability in PEF significantly increased during the 4-week treatment period in 14 patients with GlyGly16, but not in 15 patients with ArgArg16 and ArgGly16 ( = 0.032). The FEV1 slope of the dose-response curve to salbutamol decreased after the 4-week treatment period in GlyGly16, but not in pooled ArgArg16 and ArgGly16 patients. This study provides preliminary evidence that tolerance to formoterol develops more frequently in asthmatics with GlyGly16 genotype. If confirmed in a larger population, this finding might be useful in choosing the bronchodilator therapy on the basis of genetic polymorphism of the beta2-AR.

Oxidative stress and cellular pathways of asthma and inflammation: Therapeutic strategies and pharmacological targets

“…The β2-adrenergic receptor agonists act by binding to the β2-adrenergic receptor, a G-protein-coupled receptor protein encoded by ADRβ2 gene, which is expressed on multiple airway cell types (Ortega, Hawkins, Peters, & Bleecker, 2007). ADRβ2 is a highly polymorphic gene that can influence lung function, and also respond to β-agonist therapy (Fuso, et al, 2013; Green, Turki, Bejarano, Hall, & Liggett, 1995; Hawkins, et al, 2006; Martinez, Graves, Baldini, Solomon, & Erickson, 1997; Tan, Hall, Dewar, Dow, & Lipworth, 1997). Similarly, drugs targeting leukotriene signaling pathways are shown to decrease asthmatic exacerbations when coupled with corticosteroid therapy (Camargo, et al, 2010; Camargo, Smithline, Malice, Green, & Reiss, 2003; Dahlen, 2006; Philip, et al, 2010).…”

Influência dos polimorfismos no receptor beta 2 adrenérgico na presença de broncoespasmo induzido pelo exercício em adolescentes

“…ADRB2 act through mediation by adrenaline and noradrenaline action and promote smooth muscle relaxation, even in the pulmonary region,11 as well as playing an important role in bronchodilation during exercise in healthy individuals 12. The Arg16Gly and Gln27Glu polymorphisms of the ADRB2 gene have been associated with asthma symptoms,7 including reduction in the pulmonary function and in the bronchodilation response to medication, as they have negative influence on the bronchodilator effect,13 a therapeutic resource that is part of pre-exercise EIB prevention 14…”

“…Os ADRB2 atuam mediados pela ação da adrenalina e da noradrenalina e promovem o relaxamento do músculo liso, até na região pulmonar,11 além de desempenhar papel importante na broncodilatação durante o exercício em indivíduos saudáveis 12. Os polimorfismos Arg16Gly e Gln27Glu do gene do ADRB2 vêm sendo relacionados a sintomas da asma,7 incluindo a redução da função pulmonar e da resposta broncodilatadora à medicação, pois têm influência negativa no efeito da medicação broncodilatadora,13 recurso terapêutico que faz parte da prevenção do BIE pré-exercício 14…”

Influence of polymorphisms of the beta-2 adrenergic receptor on the presence of exercise-induced bronchospasm in adolescents

“… 10 ADRB2 act through mediation by adrenaline and noradrenaline action and promote smooth muscle relaxation, even in the pulmonary region, 11 as well as playing an important role in bronchodilation during exercise in healthy individuals. 12 The Arg16Gly and Gln27Glu polymorphisms of the ADRB2 gene have been associated with asthma symptoms, 7 including reduction in the pulmonary function and in the bronchodilation response to medication, as they have negative influence on the bronchodilator effect, 13 a therapeutic resource that is part of pre-exercise EIB prevention. 14 …”

“… 10 Os ADRB2 atuam mediados pela ação da adrenalina e da noradrenalina e promovem o relaxamento do músculo liso, até na região pulmonar, 11 além de desempenhar papel importante na broncodilatação durante o exercício em indivíduos saudáveis. 12 Os polimorfismos Arg16Gly e Gln27Glu do gene do ADRB2 vêm sendo relacionados a sintomas da asma, 7 incluindo a redução da função pulmonar e da resposta broncodilatadora à medicação, pois têm influência negativa no efeito da medicação broncodilatadora, 13 recurso terapêutico que faz parte da prevenção do BIE pré-exercício. 14 …”