ADRB2 haplotypes and asthma exacerbations in children and young adults: An individual participant data meta‐analysis

Abstract

Background The polymorphism Arg16 in β2‐adrenergic receptor (ADRB2) gene has been associated with an increased risk of exacerbations in asthmatic children treated with long‐acting β2‐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, I2 = 0.0%) and Arg16/Gln27 versus Gly16/Gln27 (OR: 1.43, 95% CI: 1.05–1.94, I2 = 0.0%), but not Gly16/Gln27 versus Gly16/Glu27 (OR: 0.99, 95% CI: 0.71–1.39, I2 = 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 β2‐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.

Evaluation value and mechanism of ADRB2 and FCER1B gene polymorphisms in preterm infants with congenital respiratory diseases

“…However, the results of various reports are not completely consistent. For example, Karimi L et al found that the polymorphism of Arg16Cly and GI27Glu loci of the ADRB2 gene is related to asthma susceptibility (17). Zhang YQ et al also believed that the polymorphism of the Arg16Cly locus of the ADRB2 gene may be a determinant of asthma severity and response to salbutamol (18).…”

Stimulation of Sympathetic Nerve Using Ultraflexible Cuff Electrodes Inhibits Inflammation Caused by Tendon Rupture

“…Previous studies have shown that Adrb2 exerts antiinflammatory effects. [35][36][37] Thus, we deduced that ES caused the release of NE from SchG, and NE decreased inflammation after tendon injury through Adrb2.…”

The state of studying the polymorphism of individual genes in the development of bronchial asthma

“…Передусім шанси реалізації генетично-детермінованої патології оцінюються з обов'язковим урахуванням впливу довкілля. Адже для кожного етнічного поселення, клімато-географічних параметрів місця проживання, особливостей харчових вподобань, частоти близько родинних шлюбів, культури ведення сільського господарства, темпів урбанізації тощо, частота мутантних, мажорних, мінорних алелів є різною [10,11,16,21]. Саме цим і пояснюється різна частота окремих спадково обумовлених хвороб у різних частинах світу.…”