ADRB2 haplotypes and asthma exacerbations in children and young adults: An individual participant data meta-analysis.
ADRB2
asthma exacerbations
haplotypes
inhaled corticosteroids
long-acting β2-agonists
Journal
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
ISSN: 1365-2222
Titre abrégé: Clin Exp Allergy
Pays: England
ID NLM: 8906443
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
25
05
2021
received:
27
08
2020
accepted:
28
05
2021
pubmed:
16
6
2021
medline:
24
3
2022
entrez:
15
6
2021
Statut:
ppublish
Résumé
The polymorphism Arg16 in β We assessed whether the haplotype analysis could explain the association between the polymorphisms at codons 16 (Arg16Gly) and 27 (Gln27Glu) in ADRB2 and risk of asthma exacerbations in patients treated with inhaled corticosteroids (ICS) plus LABA. The study was undertaken using data from 10 independent studies (n = 5903) participating in the multi-ethnic Pharmacogenomics in Childhood Asthma (PiCA) consortium. Asthma exacerbations were defined as asthma-related use of oral corticosteroids or hospitalizations/emergency department visits in the past 6 or 12 months prior to the study visit/enrolment. The association between the haplotypes and the risk of asthma exacerbations was performed per study using haplo.stats package adjusted for age and sex. Results were meta-analysed using the inverse variance weighting method assuming random-effects. In subjects treated with ICS and LABA (n = 832, age: 3-21 years), Arg16/Gln27 versus Gly16/Glu27 (OR: 1.40, 95% CI: 1.05-1.87, I The ADRB2 Arg16 haplotype, presumably mainly driven by the Arg16, increased the risk of asthma exacerbations in patients treated with ICS plus LABA. This finding could be beneficial in ADRB2 genotype-guided treatment which might improve clinical outcomes in asthmatic patients.
Sections du résumé
BACKGROUND
The polymorphism Arg16 in β
OBJECTIVE
We assessed whether the haplotype analysis could explain the association between the polymorphisms at codons 16 (Arg16Gly) and 27 (Gln27Glu) in ADRB2 and risk of asthma exacerbations in patients treated with inhaled corticosteroids (ICS) plus LABA.
METHODS
The study was undertaken using data from 10 independent studies (n = 5903) participating in the multi-ethnic Pharmacogenomics in Childhood Asthma (PiCA) consortium. Asthma exacerbations were defined as asthma-related use of oral corticosteroids or hospitalizations/emergency department visits in the past 6 or 12 months prior to the study visit/enrolment. The association between the haplotypes and the risk of asthma exacerbations was performed per study using haplo.stats package adjusted for age and sex. Results were meta-analysed using the inverse variance weighting method assuming random-effects.
RESULTS
In subjects treated with ICS and LABA (n = 832, age: 3-21 years), Arg16/Gln27 versus Gly16/Glu27 (OR: 1.40, 95% CI: 1.05-1.87, I
CONCLUSION AND CLINICAL RELEVANCE
The ADRB2 Arg16 haplotype, presumably mainly driven by the Arg16, increased the risk of asthma exacerbations in patients treated with ICS plus LABA. This finding could be beneficial in ADRB2 genotype-guided treatment which might improve clinical outcomes in asthmatic patients.
Identifiants
pubmed: 34128573
doi: 10.1111/cea.13965
pmc: PMC8503671
mid: NIHMS1734494
doi:
Substances chimiques
ADRB2 protein, human
0
Receptors, Adrenergic, beta-2
0
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1157-1171Subventions
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : R-154-000-A95-592
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : BMRC/01/1/21/18/077
Organisme : Brighton and Sussex Medical School
Organisme : National Medical Research Council (NMRC) (Singapore)
Organisme : National Heart, Lung, and Blood Institute of the National Institute of Health (NIH)
ID : X01 HL134589
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : SIgN-06-006
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : R-154-000-553-112
Organisme : Singapore Ministry of Education Academic Research Fund
Organisme : National Institute for Health Research (NIHR)
Organisme : NHLBI NIH HHS
ID : R01 HL117004
Pays : United States
Organisme : Perth and Kinross Council
Organisme : NIEHS NIH HHS
ID : R01 ES015794
Pays : United States
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : H17/01/a0/008
Organisme : American Asthma Foundation
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : R-154-000-191-112
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : N-154-000-038-001
Organisme : Alder Hey Clinical Research Facility
Organisme : UK Department of Health
Organisme : German charity Atemwegsliga
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : R-154-000-404-112
Organisme : Gannochy Trust
Organisme : Instituto de Salud Carlos III (ISCIII)
ID : AC15/00015
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : R-154-000-A91-592
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : BMRC/04/1/21/19/315
Organisme : German Ministry of Science and Education
ID : 01ZX1306E
Organisme : National Heart, Lung, and Blood Institute of the National Institute of Health (NIH)
ID : R01HL117004
Organisme : Slovenian Research Agency
ID : P3-0067
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : R-154-000-565-112
Organisme : GSK (part of a strategic alliance between GSK and Utrecht Institute for Pharmaceutical Sciences (UIPS))
Organisme : Netherlands Organization for Health Research and Development
ID : 113201006
Organisme : Scottish Enterprises Tayside
Organisme : European Community (EC)
Organisme : SysPharmPedia
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : R-154-000-A27-597
Organisme : Instituto de Salud Carlos III (ISCIII)
ID : FI16/00136
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : R-154-000-630-112
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : NMRC/1150/2008
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : R154-000-B99-114
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : R-154-000-A08-592
Organisme : European Union under the Horizon 2020
Organisme : Spanish Ministry of Economy, Industry, and Competitiveness
Organisme : Ministry of Education, Science and Sport of the Republic of Slovenia
ID : C3330-16-500106
Organisme : Singapore Immunology Network
Organisme : Sandler Family Foundation
Organisme : Chief Scientist Office
ID : CZH/4/418
Pays : United Kingdom
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : SIgN-08-020
Organisme : Agency for Science Technology and Research (A*STAR) (Singapore)
ID : APG2013/108
Organisme : RWJF Amos Medical Faculty Development Program
Organisme : Ramón y Cajal Program
ID : RYC-2015-17205
Informations de copyright
© 2021 John Wiley & Sons Ltd.
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