title: ADRB2 Gly16Arg polymorphism, asthma control and lung function decline.
abstract: Arg/Arg homozygotes for the Gly16Arg polymorphism in the β₂-adrenoreceptor gene (ADRB2) have a reduced response to short-acting β₂-agonists but no effect has been associated with long-acting β₂-agonists (LABAs). We selected 604 subjects with current asthma from the European Community Respiratory Health Study to evaluate whether asthma control and lung function decline were associated with Gly16Arg polymorphism, and to test whether LABA or inhaled corticosteroid (ICS) use modified these effects. There was an increased risk of noncontrolled asthma (OR 1.33, 95% CI 1.01-1.75; p = 0.046) for each Arg allele. Among nonusers of ICS, the odds ratio of noncontrolled asthma among Arg/Arg versus Gly/Gly subjects was 2.73 (95% CI 1.28-5.82; p = 0.009). No increased risk of noncontrolled asthma associated with the Arg allele was observed among ICS and/or LABA users. For each Arg allele, a mean ± se decrease in decline in forced expiratory volume in 1 s of 7.7 ± 2.5 mL·yr⁻¹ was found (p-value for trend 0.003), irrespective of ICS or LABA use. Arg/Arg subjects had an increased risk of bronchial hyperresponsiveness (BHR) versus Gly/Gly subjects, with an odds ratio of 2.51 (95% CI 1.12-5.63; p = 0.025) if they did not use ICS. The Arg allele was associated with poorer asthma control, a steeper lung function decline and BHR. Absence of genotypic effects on asthma control among ICS users may be due to reversed β₂-adrenoreceptor desensitisation.
authors: Centre for Research in Environmental Epidemiology, Hospital del Mar Research Institute (IMIM), Barcelona, Spain. crebordo@email.arizona.edu
authors: C
authors: C
authors: Rebordosa
authors: M
authors: M
authors: Kogevinas
authors: S
authors: S
authors: Guerra
authors: F
authors: F
authors: Castro-Giner
authors: D
authors: D
authors: Jarvis
authors: L
authors: L
authors: Cazzoletti
authors: I
authors: I
authors: Pin
authors: V
authors: V
authors: Siroux
authors: M
authors: M
authors: Wjst
authors: J M
authors: JM
authors: Antò
authors: R
authors: R
authors: de Marco
authors: X
authors: X
authors: Estivill
authors: A G
authors: AG
authors: Corsico
authors: R
authors: R
authors: Nielsen
authors: C
authors: C
authors: Janson
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use; D000328:Adult; D000483:Alleles; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity; D003692:Delayed-Action Preparations; D005260:Female; D005541:Forced Expiratory Volume; D005838:Genotype; D005938:Glucocorticoids / Q000008:administration & dosage; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012129:Respiratory Function Tests
chemical_list: C553443:ADRB2 protein, human; D058666:Adrenergic beta-2 Receptor Agonists; D003692:Delayed-Action Preparations; D005938:Glucocorticoids; D018343:Receptors, Adrenergic, beta-2