ArticleAmerican journal of physiology. Lung cellular and molecular physiology2008
Variable-length poly-C tract polymorphisms of the beta2-adrenergic receptor 3'-UTR alter expression and agonist regulation.
Article in American journal of physiology. Lung cellular and molecular physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 21 citations in OpenAlex.
- Effect of β2-adrenergic receptor gene (ADRB2) 3' untranslated region polymorphisms on inhaled corticosteroid/long-acting β2-adrenergic agonist response.Respiratory research · 2012Trial
- A CREB-mediated increase in miRNA let-7f during prolonged β-agonist exposure: a novel mechanism of βFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- An environmental epigenetic study of ADRB2 5'-UTR methylation and childhood asthma severity.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2012Article
- Common ADRB2 haplotypes derived from 26 polymorphic sites direct beta2-adrenergic receptor expression and regulation phenotypes.PloS one · 2010Article
- Evolutionary history of the ADRB2 gene in humans.American journal of human genetics · 2010Article
- The role of pharmacogenomics in improving the management of asthma.The Journal of allergy and clinical immunology · 2010Review
- The pharmacogenetics of asthma treatment.Current allergy and asthma reports · 2009Review
- Pharmacogenetics of asthma.Current opinion in pulmonary medicine · 2009Review
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7 authors at 3 institutions in 1 country.
Funding
Abstract
Beta(2)-adrenergic receptors (beta(2)-AR) expressed on airway epithelial and smooth muscle cells regulate mucociliary clearance and relaxation and are the targets for beta-agonists in the treatment of obstructive lung disease. However, the clinical responses display extensive interindividual variability, which is not adequately explained by genetic variability in the 5'-flanking or coding region of the intronless beta(2)-AR gene. The nonsynonymous coding polymorphism most often associated with a bronchodilator phenotype (Arg16) is found within three haplotypes that differ by the number of Cs (11, 12, or 13) within a 3'-untranslated region (UTR) poly-C tract. To examine potential effects of this variability on receptor expression, BEAS-2B cells were transfected with constructs containing the beta(2)-AR (Arg16) coding sequence followed by its 3'-UTR with the various polymorphic poly-C tracts. beta(2)Arg16-11C had 25% lower mRNA expression and 33% lower beta(2)-AR protein expression compared with the other two haplotypes. Consistent with this lower steady-state expression, beta(2)Arg16-11C mRNA displayed more rapid and extensive degradation after actinomycin D treatment compared with beta(2)Arg16-12C and -13C. However, beta(2)Arg16-12C underwent 50% less downregulation of receptor expression during beta-agonist exposure compared with the other two haplotypes. Thus these haplotypes direct a potential low-response phenotype due to decreased steady-state receptor expression combined with wild-type agonist-promoted downregulation (beta(2)Arg16-11C) and a high-response phenotype due to increased baseline expression combined with decreased agonist-promoted downregulation (beta(2)Arg16-12C). This heterogeneity may contribute to the variability of clinical responses to beta-agonist, and genotyping to identify these 3'-UTR polymorphisms may improve predictive power within the context of beta(2)-AR haplotypes in pharmacogenetic studies.
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