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J Clin Med. 2019 Nov 1;8(11). pii: E1835. doi: 10.3390/jcm8111835.

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

Author information

1
Department of Medical Informatics, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. l.karimi@erasmusmc.nl.
2
Department of Bioanalysis, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. lies.lahousse@ugent.be.
3
Department of Epidemiology, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. lies.lahousse@ugent.be.
4
Department of Epidemiology, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. m.ghanbari@erasmusmc.nl.
5
Department of Genetics, School of Medicine, Mashhad University of Medical Science, 9177899191 Mashhad, Iran. m.ghanbari@erasmusmc.nl.
6
Department of Epidemiology, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. n.terzikhan@erasmusmc.nl.
7
Department of Respiratory Medicine, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium. n.terzikhan@erasmusmc.nl.
8
Department of Internal Medicine, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. a.g.uitterlinden@erasmusmc.nl.
9
Department of Medical Informatics, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. j.vanderlei@erasmusmc.nl.
10
Department of Epidemiology, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. Guy.Brusselle@uzgent.be.
11
Department of Respiratory Medicine, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium. Guy.Brusselle@uzgent.be.
12
Department of Respiratory Medicine, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. Guy.Brusselle@uzgent.be.
13
Department of Epidemiology, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. b.stricker@erasmusmc.nl.
14
Department of Internal Medicine, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. b.stricker@erasmusmc.nl.
15
Department of Medical Informatics, Erasmus University Medical Center, Doctor Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. k.verhamme@erasmusmc.nl.
16
Department of Bioanalysis, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. k.verhamme@erasmusmc.nl.

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 1,053 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 categorised 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.

KEYWORDS:

ADRB2 gene; chronic obstructive pulmonary disease; exacerbations; inhaled β2-agonists

PMID:
31683975
DOI:
10.3390/jcm8111835
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Conflict of interest statement

The authors declare no conflict of interest related to this manuscript.

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