ADRB2 Gly16Arg polymorphism, asthma control and lung function decline

C. Rebordosa, M. Kogevinas, S. Guerra, F. Castro-Giner, D. Jarvis, L. Cazzoletti, I. Pin, V. Siroux, M. Wjst, J. M. Antò, R. De Marco, X. Estivill, A. G. Corsico, R. Nielsen, C. Janson

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Arg/Arg homozygotes for the Gly16Arg polymorphism in the β 2-adrenoreceptor gene (ADRB2) have a reduced response to short-acting β 2-agonists but no effect has been associated with long-acting β 2-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 β 2-adrenoreceptor desensitisation.

Original languageEnglish (US)
Pages (from-to)1029-1035
Number of pages7
JournalEuropean Respiratory Journal
Volume38
Issue number5
DOIs
StatePublished - Nov 1 2011

Keywords

  • Asthma control
  • Bronchial hyperresponsiveness
  • Corticosteroids
  • Lung function
  • β -adrenoreceptor polymorphisms

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Rebordosa, C., Kogevinas, M., Guerra, S., Castro-Giner, F., Jarvis, D., Cazzoletti, L., Pin, I., Siroux, V., Wjst, M., Antò, J. M., De Marco, R., Estivill, X., Corsico, A. G., Nielsen, R., & Janson, C. (2011). ADRB2 Gly16Arg polymorphism, asthma control and lung function decline. European Respiratory Journal, 38(5), 1029-1035. https://doi.org/10.1183/09031936.00146310