Recent advances in asthma

Barnes, Peter J.; Lee, T. H.

doi:10.1136/pgmj.68.806.942

Cited by 17 publications

(10 citation statements)

References 129 publications

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“…The ␤ 2 -adrenergic agonists are the most potent bronchodilators presently available for the treatment of asthma (1). These drugs are not only widely prescribed for mild asthmatic symptoms, but are also the main pharmacologic tool used to relieve bronchoconstriction during acute, life-threatening asthmatic attacks.…”

Section: Introductionmentioning

confidence: 99%

“…Reihsaus et al ( 4) recently described nine polymorphisms in the ␤ 2 -adrenergic receptor ( ␤ 2 AR) 1 gene, of which two were more frequent and gave rise to amino acid exchanges in the putative extracellular amino-terminus region of the gene: ␤ 2 AR-16, with replacement of arginine (Arg-16) for glycine (Gly-16); and ␤ 2 AR-27, with replacement of glutamine (Gln-27) for glutamic acid (Glu-27). There was no relation between ␤ 2 AR polymorphisms and asthma prevalence, but the Gly-16 variant was apparently associated with a more severe form of the disease (4).…”

Section: Introductionmentioning

confidence: 99%

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Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing.

et al. 1997

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The beta2-adrenergic receptor (beta2AR) agonists are the most widely used agents in the treatment of asthma, but the genetic determinants of responsiveness to these agents are unknown. Two polymorphic loci within the coding region of the beta2AR have been recently described at amino acids 16 and 27. It has been reported that glycine at codon 16 (Gly-16) is associated with increased agonist-promoted downregulation of the beta2AR as compared with arginine-16 (Arg-16). The form of the receptor with glutamic acid at codon 27 (Glu-27), on the other hand, has been shown to be resistant to downregulation when compared with glutamine-27 (Gln-27), but only when coexpressed with Arg-16. To assess if different genotypes of these two polymorphisms would show differential responses to inhaled beta2AR agonists, we genotyped 269 children who were participants in a longitudinal study of asthma. Spirometry was performed before and after administration of 180 microg of albuterol, and a positive response was considered an increase of >15.3% predicted FEV1. There was marked linkage disequilibrium between the two polymorphisms, with 97.8% of all chromosomes that carried Arg-16 also carrying Gln-27. When compared to homozygotes for Gly-16, homozygotes for Arg-16 were 5.3 times (95% confidence interval 1.6-17.7) and heterozygotes for beta2AR-16 were 2.3 times (1.3-4.2) more likely to respond to albuterol, respectively. Similar trends were observed for asthmatic and nonasthmatic children, and results were independent of baseline lung function, ethnic origin, and previous use of antiasthma medication. No association was found between the beta2AR-27 polymorphism and response to albuterol. These results may explain some of the variability in response to therapeutic doses of albuterol in children.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing.

et al. 1997

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“…In the early 1990s, a classification scheme was developed for defining asthma severity and choosing appropriate treatment regimens [2]. Reliever drugs, such as inhaled short‐acting β‐agonists, are the most commonly prescribed asthma medications in the world [3]. These drugs are not only widely prescribed for mild asthmatic symptoms, but are also the main pharmacologic tool used to relieve bronchoconstriction during acute, life‐threatening asthmatic attacks.…”

Section: Introductionmentioning

confidence: 99%

Association between bronchodilating response to short‐acting β‐agonist and non‐synonymous single‐nucleotide polymorphisms of β₂‐adrenoceptor gene

Cho

Bahn

et al. 2005

Clin Experimental Allergy

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“…The projected economic burden of uncontrolled asthma in the US alone is estimated to be 300 billion dollars over the next 20 years [ 2 ]. Asthma is often treated with β2-agonists (e.g., albuterol), to relieve acute bronchoconstriction [ 3 ]. β2-Agonists reduce bronchoconstriction by stimulating the β2-adrenergic receptors (β2ARs) on airway smooth muscle.…”

Section: Introductionmentioning

confidence: 99%

Age by Single Nucleotide Polymorphism Interactions on Bronchodilator Response in Asthmatics

Voorhies

Sordillo

McGeachie

et al. 2021

JPM

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An unaddressed and important issue is the role age plays in modulating response to short acting β2-agonists in individuals with asthma. The objective of this study was to identify whether age modifies genetic associations of single nucleotide polymorphisms (SNPs) with bronchodilator response (BDR) to β2-agonists. Using three cohorts with a total of 892 subjects, we ran a genome wide interaction study (GWIS) for each cohort to examine SNP by age interactions with BDR. A fixed effect meta-analysis was used to combine the results. In order to determine if previously identified BDR SNPs had an age interaction, we also examined 16 polymorphisms in candidate genes from two published genome wide association studies (GWAS) of BDR. There were no significant SNP by age interactions on BDR using the genome wide significance level of 5 × 10−8. Using a suggestive significance level of 5 × 10−6, three interactions, including one for a SNP within PRAG1 (rs4840337), were significant and replicated at the significance level of 0.05. Considering candidate genes from two previous GWAS of BDR, three SNPs (rs10476900 (near ADRB2) [p-value = 0.009], rs10827492 (CREM) [p-value = 0.02], and rs72646209 (NCOA3) [p-value = 0.02]) had a marginally significant interaction with age on BDR (p < 0.05). Our results suggest age may be an important modifier of genetic associations for BDR in asthma.

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Recent advances in asthma

Cited by 17 publications

References 129 publications

Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing.

Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing.

Association between bronchodilating response to short‐acting β‐agonist and non‐synonymous single‐nucleotide polymorphisms of β₂‐adrenoceptor gene

Age by Single Nucleotide Polymorphism Interactions on Bronchodilator Response in Asthmatics

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Recent advances in asthma

Cited by 17 publications

References 129 publications

Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing.

Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing.

Association between bronchodilating response to short‐acting β‐agonist and non‐synonymous single‐nucleotide polymorphisms of β2‐adrenoceptor gene

Age by Single Nucleotide Polymorphism Interactions on Bronchodilator Response in Asthmatics

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Product

Resources

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Association between bronchodilating response to short‐acting β‐agonist and non‐synonymous single‐nucleotide polymorphisms of β₂‐adrenoceptor gene