TY - JOUR
T1 - ADRB2 haplotypes and risk of exacerbations in asthmatic children and young adults treated with long-acting beta 2-agonists
T2 - A meta-analysis in the PiCA consortium
AU - Karimi, Leila
AU - Vijverberg, Susanne J.
AU - Engelkes, Marjolein
AU - Hernandez-Pacheco, Natalia
AU - Farzan, Niloufar
AU - Soares, Patricia
AU - Francis, Ben R.
AU - Pino-Yanes, Maria
AU - Eng, Celeste
AU - Mukhopadhyay, Somnath
AU - Schieck, Maximilian
AU - Kabesch, Michael
AU - Burchard, Esteban G.
AU - Palmer, Colin N. A.
AU - Turner, Steve W.
AU - Janssens, Hettie M.
AU - Maitland-Van Der Zee, Anke-Hilse
AU - Verhamme, Katia M. C.
PY - 2019/11/21
Y1 - 2019/11/21
N2 - 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.
AB - 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.
KW - Asthma
KW - Genetics
KW - Exacerbation
U2 - 10.1183/13993003.congress-2019.PA5388
DO - 10.1183/13993003.congress-2019.PA5388
M3 - Meeting abstract
SN - 0903-1936
VL - 54
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 63
M1 - PA5388
ER -