ADRB2 haplotypes and risk of exacerbations in asthmatic children and young adults treated with long-acting beta 2-agonists: A meta-analysis in the PiCA consortium

Leila Karimi, Susanne J. Vijverberg, Marjolein Engelkes, Natalia Hernandez-Pacheco, Niloufar Farzan, Patricia Soares, Ben R. Francis, Maria Pino-Yanes, Celeste Eng, Somnath Mukhopadhyay, Maximilian Schieck, Michael Kabesch, Esteban G. Burchard, Colin N. A. Palmer, Steve W. Turner, Hettie M. Janssens, Anke-Hilse Maitland-Van Der Zee, Katia M. C. Verhamme

Research output: Contribution to journalMeeting abstractpeer-review

Abstract

Background: The association of haplotype combinations of polymorphisms at positions 16 and 27 of the β2-adrenergic receptor (ADRB2) gene and the risk of asthma exacerbations among users of long-acting β2-agonists (LABA) is still unclear. Aim: We investigated the association between these haplotypes of the ADRB2 gene and asthma exacerbations in asthmatic patients using LABA and inhaled corticosteroids (ICS) from the multi-ethnic Pharmacogenomics in Childhood Asthma (PiCA) consortium. Methods: We conducted a meta-analysis of 880 children and young adults aged (4-21) with asthma treated with LABA and ICS. We extracted two polymorphisms; rs1042713 (16Arg>Gly) and rs1042714 (27Gln>Glu) in the ADRB2 gene. Asthma exacerbations were defined as prescribed courses of oral corticosteroids and/or asthma-related hospitalizations/emergency room visits in the past 6 or 12 months prior to the study visit. The association between the haplotypes and asthma exacerbations was performed by using the Haplo-Stats package adjusted for age and sex. A meta-analysis was performed using an inverse variance–weighted method assuming a random-effect. Results: Three haplotypes were determined; Gly16Glu27, Arg16Gln27 and Gly16Gln27. Compared to the Gly16Glu27 haplotype, the Arg16Gln27 haplotype was significantly associated with an increased risk of asthma exacerbations (OR:1.37, 95%CI;1.03-1.81, P=0.028, I2=0.0%). Conclusion: We found that the Arg haplotype (Arg16Gln27) in the ADRB2 gene increased the risk of exacerbations among users of LABA and ICS. Whether or not this argues against use of LABA in patients with this haplotype needs further research.
Original languageEnglish
Article numberPA5388
JournalEuropean Respiratory Journal
Volume54
Issue number63
Early online date28 Sep 2019
DOIs
Publication statusPublished - 21 Nov 2019

Keywords

  • Asthma
  • Genetics
  • Exacerbation

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