Karimi, Leila and Vijverberg, Susanne J. and Engelkes, Marjolein and Hernandez-Pacheco, Natalia and Farzan, Niloufar and Soares, Patricia and Pino-Yanes, Maria and Jorgensen, Andrea L. and Eng, Celeste and Mukhopadhyay, Somnath and Schieck, Maximilian and Kabesch, Michael and Burchard, Esteban G. and Chew, Fook Tim and Sio, Yang Yie and Gorenjak, Mario and Hawcutt, Daniel B. and Palmer, Colin N. and Turner, Steve and Janssens, Hettie M. and Maitland-van der Zee, Anke H. and Verhamme, Katia M. C. (2021) ADRB2 haplotypes and asthma exacerbations in children and young adults: An individual participant data meta-analysis. CLINICAL AND EXPERIMENTAL ALLERGY, 51 (9). pp. 1157-1171. ISSN 0954-7894, 1365-2222
Full text not available from this repository. (Request a copy)Abstract
Background The polymorphism Arg16 in beta(2)-adrenergic receptor (ADRB2) gene has been associated with an increased risk of exacerbations in asthmatic children treated with long-acting beta(2)-agonists (LABA). However, it remains unclear whether this increased risk is mainly attributed to this single variant or the combined effect of the haplotypes of polymorphisms at codons 16 and 27. 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-2 = 0.0%) and Arg16/Gln27 versus Gly16/Gln27 (OR: 1.43, 95% CI: 1.05-1.94, I-2 = 0.0%), but not Gly16/Gln27 versus Gly16/Glu27 (OR: 0.99, 95% CI: 0.71-1.39, I-2 = 0.0%), were significantly associated with an increased risk of asthma exacerbations. The sensitivity analyses indicated no significant association between the ADRB2 haplotypes and asthma exacerbations in the other treatment categories, namely as-required short-acting beta(2)-agonists (n = 973), ICS monotherapy (n = 2623), ICS plus leukotriene receptor antagonists (LTRA; n = 338), or ICS plus LABA plus LTRA (n = 686). 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BETA-AGONIST; INHALED CORTICOSTEROIDS; PRECISION MEDICINE; ORMDL3 EXPRESSION; AIR-POLLUTION; LUNG-FUNCTION; GALA II; POLYMORPHISMS; GENOTYPE; RISK; ADRB2; asthma exacerbations; haplotypes; inhaled corticosteroids; long-acting beta(2)-agonists |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Sep 2022 14:18 |
| Last Modified: | 30 Sep 2022 14:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48159 |
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