ADRB2 Gly16Arg polymorphism, asthma control and lung function decline.

Arg/Arg homozygous for the Gly16Arg polymorphism in ADRB2 have a reduced response to short acting β2-agonists but no effect has been associated with long-acting β2-agonists (LABA). We selected 604 subjects from the European Community Respiratory Health Study with current asthma to evaluate if asthma control and lung function decline were associated with Gly16Arg polymorphism and test if LABA or inhaled corticosteroids (ICS) use modified these effects. There was an increased risk of non-controlled asthma OR=1.33 (1.01-1.75, p=0.046) for each Arg allele. Among nonusers of ICS, the risk of non-controlled asthma among Arg/Arg vs. Gly/Gly subjects was OR=2.73 (1.28-5.82, p=0.009). No increased risk of non-controlled asthma associated to the Arg allele was observed among ICS and/or LABA users. For each Arg allele a decrease of 7.7 mL·year(-1) (SE 2.5) in FEV1 decline was found (p-trend=0.003), irrespective of ICS or LABA use. Arg/Arg subjects vs. Gly/Gly subjects had an increased risk of bronchial hyperresponsiveness with an OR of 2.51 (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 bronchial hyperresponsiveness. Absence of genotypic effects on asthma control among ICS users may be due to reversed ADRB2 desensitization.