β2-Adrenergic Receptor (ADRB2) Gene Polymorphisms and Risk of COPD Exacerbations: The Rotterdam Study.

Leila Karimi,Johan Van Der Lei,André G Uitterlinden,Bruno H Stricker,Mohsen Ghanbari,Katia M C Verhamme,Natalie Terzikhan,Lies Lahousse,Guy G Brusselle

doi:10.3390/jcm8111835

Abstract

The role of the β2-adrenergic receptor (ADRB2) gene in patients with chronic obstructive pulmonary disease (COPD) is unclear. We investigated the association between ADRB2 variants and the risk of exacerbations in COPD patients treated with inhaled β2-agonists. Within the Rotterdam Study, a population-based cohort study, we followed 1053 COPD patients until the first COPD exacerbation or end of follow-up and extracted rs1042713 (16Arg > Gly) and rs1042714 (27Gln > Glu) in ADRB2. Exposure to inhaled β2-agonists was categorized into current, past, or non-use on the index date (date of COPD exacerbation for cases and on the same day of follow-up for controls). COPD exacerbations were defined as acute episodes of worsening symptoms requiring systemic corticosteroids and/or antibiotics (moderate exacerbations), or hospitalization (severe exacerbations). The associations between ADRB2 variants and COPD exacerbations were assessed using Cox proportional hazards models, adjusting for age, sex, use of inhaled corticosteroids, daily dose of β2-agonists, and smoking. In current users of β2-agonists, the risk of COPD exacerbation decreased by 30% (hazard ratio (HR); 0.70, 95% CI: 0.59–0.84) for each copy of the Arg allele of rs1042713 and by 20% (HR; 0.80, 95% CI: 0.69–0.94) for each copy of the Gln allele of rs1042714. Furthermore, current users carrying the Arg16/Gln27 haplotype had a significantly lower risk (HR; 0.70, 95% CI: 0.59–0.85) of COPD exacerbation compared to the Gly16/Glu27 haplotype. In conclusion, we observed that the Arg16/Gln27 haplotype in ADRB2 was associated with a reduced risk of COPD exacerbation in current users of inhaled β2-agonists.

Highlights

Chronic Obstructive Pulmonary Disease (COPD) is a common disease, which is characterized by a persistent expiratory airflow limitation that is usually progressive [1]
Rs1042713: patients with Arg/Arg genotype required more frequent treatment with antibiotics, as well as systemic corticosteroid therapy. rs1042714: no association rs1042713: no association reported rs1042714: no association reported. In this population-based cohort study, we observed that ADRB2 polymorphisms: rs1042713 and rs1042714 were associated with a reduced risk of COPD exacerbation in current users of inhaled β2-agonists
To the best of our knowledge, this is the first population-based study assessing the association between ADRB2 polymorphisms and COPD exacerbations in patients with COPD treated with inhaled β2-agonists

Summary

Introduction

Chronic Obstructive Pulmonary Disease (COPD) is a common disease, which is characterized by a persistent expiratory airflow limitation that is usually progressive [1]. Inhaled β2-receptor agonists are one of the main classes of bronchodilators used to treat airflow obstruction [1]. Multiple single nucleotide polymorphisms (SNPs) in this gene have been described [2]. Two of these SNPs code for amino acid changes at positions 16 [arginine to glycine (16Arg > Gly); rs1042713] and 27 [glutamine to glutamic acid (27Gln > Glu); rs1042714], both of which are common variants and have previously been studied [4,5]

Methods

Results

Conclusion