Association between β2-adrenoceptor polymorphism and susceptibility to bronchodilator desensitisation in moderately severe stable asthmatics

Tan, Soong; Hall, Ian P.; Dewar, J.; Dow, Ellie; Lipworth, Brian J.

doi:10.1016/s0140-6736(97)03211-x

Cited by 318 publications

(218 citation statements)

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“…Conversely, a study by Tan et al (1997) found significantly greater bronchodilator desensitisation in Gly16 homozygotes. However, some studies have not found any evidence of an effect of the b 2 AR polymorphisms on response to b 2 -agonist therapy (Hancox et al 1998;Lipworth et al 1999).…”

Section: Discussionmentioning

confidence: 85%

β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults

et al. 2006

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The b 2 -adrenergic receptor (b 2 AR) is a transmembrane protein expressed by airway smooth muscle cells. In vitro studies have shown that polymorphisms at amino acid positions 16 and 27 alter receptor function. The aim of this study was to examine the associations between the b 2 AR polymorphisms and risks of asthma, chronic obstructive pulmonary disease (COPD) and respiratory symptoms in a sample of adults. Participants were part of a cross-sectional populationbased study of risk factors for respiratory disease. A total of 1,090 Caucasian participants completed a detailed respiratory questionnaire, spirometry, methacholine challenge and measurement of gas transfer. Genotyping for b 2 AR polymorphisms at positions 16 and 27 was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method. Haplotype frequencies for the two polymorphisms were estimated using the E-M algorithm. We found the Arg16 homozygotes had an increased risk of COPD (OR 5.13; 95% CI 1

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Section: Discussionmentioning

confidence: 85%

β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults

et al. 2006

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“…b2AR allele: 20 this phenomenon plays a role in bronchodilator desensitization 21 and in the attenuation of the vasodilatatory response to catecholamines. 22 Although these data support a role for G16 b2AR in EH, we are not aware of any molecular mechanism linking R16R b2AR and G16G b2AR homozygotes with increased BP levels.…”

Section: Genetics Ofmentioning

confidence: 99%

Genetic polymorphisms of the β-adrenergic system: association with essential hypertension and response to β-blockade

et al. 2004

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“…However, we saw a small but consistent and signi®cant reduction in transcriptional activity of the construct p0.55mutb 2 AR-LUC (c.f.`wild-type') containing one common polymorphic variant haplotype, suggesting that individuals with these polymorphisms may have reduced receptor expression. This may be relevant given the known clinical correlates of coding region polymorphisms within the b 2 adrenoceptor gene: in particular the demonstration that the glycine 16 variant of the receptor is associated with increased receptor downregulation both in vitro and in vivo and with bronchodilator subsensitivity (Tan et al, 1997;Turki et al, 1995a). However, it is important to realize that changes in levels of gene expression may not relate directly to changes in the level of receptor expression at the cell surface.…”

Section: Construction Of Luciferase Reporter Constructsmentioning

confidence: 99%

Identification of novel polymorphisms within the promoter region of the human β₂ adrenergic receptor gene

Scott

Swan

Wheatley

et al. 1999

British J Pharmacology

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107

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By screening the 1470 bp 5′ to the start codon of the human β2 adrenergic receptor gene, we have identified a total of eight polymorphisms (−20 T→C, −47 T→C, −367 T→C, −468 C→G, −654 G→A, −1023 G→A, −1343 A→G and −1429 T→A c.f. β2 adrenergic receptor start codon). Transient transfection of 5′ flanking deletion luciferase reporter constructs demonstrated the majority of activity of the human β2 adrenergic gene 5′ flanking region to be present within a 549 bp fragment immediately upstream from the start codon. Because of linkage disequilibrium, some combinations of polymorphisms were particularly frequent. We transiently transfected COS‐7 cells with luciferase constructs under the control of the 549 bp of 5′ flanking DNA containing the two most frequent extended haplotypes in this region. Luciferase activity was significantly reduced in cells transfected with the ‘mutant’ construct (−20C, −47C, −367C, −468G) c.f. the ‘wild‐type’ construct (−20T, −47T, −367T, −468C). These data suggest that polymorphisms have the potential to alter human β2 adrenergic receptor gene expression.British Journal of Pharmacology (1999) 126, 841–844; doi:10.1038/sj.bjp.0702385

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Association between β2-adrenoceptor polymorphism and susceptibility to bronchodilator desensitisation in moderately severe stable asthmatics

Cited by 318 publications

References 18 publications

β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults

β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults

Genetic polymorphisms of the β-adrenergic system: association with essential hypertension and response to β-blockade

Identification of novel polymorphisms within the promoter region of the human β₂ adrenergic receptor gene

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Association between β2-adrenoceptor polymorphism and susceptibility to bronchodilator desensitisation in moderately severe stable asthmatics

Cited by 318 publications

References 18 publications

β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults

β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults

Genetic polymorphisms of the β-adrenergic system: association with essential hypertension and response to β-blockade

Identification of novel polymorphisms within the promoter region of the human β2 adrenergic receptor gene

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Identification of novel polymorphisms within the promoter region of the human β₂ adrenergic receptor gene