Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/20851928http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20851928http://www.w3.org/2000/01/rdf-schema#comment"

Rationale

β₂-agonists, the most common treatment for asthma, have a wide interindividual variability in response, which is partially attributed to genetic factors. We previously identified single nucleotide polymorphisms in the arginase 1 (ARG1) gene, which are associated with β₂-agonist bronchodilator response (BDR).

Objectives

To identify cis-acting haplotypes in the ARG1 locus that are associated with BDR in patients with asthma and regulate gene expression in vitro.

Methods

We resequenced ARG1 in 96 individuals and identified three common, 5' haplotypes (denoted 1, 2, and 3). A haplotype-based association analysis of BDR was performed in three independent, adult asthma drug trial populations. Next, each haplotype was cloned into vectors containing a luciferase reporter gene and transfected into human airway epithelial cells (BEAS-2B) to ascertain its effect on gene expression.

Measurements and main results

BDR varied by haplotype in each of the three populations with asthma. Individuals with haplotype 1 were more likely to have higher BDR, compared to those with haplotypes 2 and 3, which is supported by odds ratios of 1.25 (95% confidence interval, 1.03-1.71) and 2.18 (95% confidence interval, 1.34-2.52), respectively. Luciferase expression was 50% greater in cells transfected with haplotype 1 compared to haplotypes 2 and 3.

Conclusions

The identified ARG1 haplotypes seem to alter BDR and differentially regulate gene expression with a concordance of decreased BDR and reporter activity from haplotypes 2 and 3. These findings may facilitate pharmacogenetic tests to predict individuals who may benefit from other therapeutic agents in addition to β(2)-agonists for optimal asthma management. Clinical trial registered with www.clinicaltrials.gov (NCT00156819, NCT00046644, and NCT00073840)."xsd:string
http://purl.uniprot.org/citations/20851928http://purl.org/dc/terms/identifier"doi:10.1164/rccm.201005-0758oc"xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/author"Liggett S.B."xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/author"Litonjua A.A."xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/author"Tantisira K.G."xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/author"Hawkins G.A."xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/author"Meyers D.A."xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/author"Duan Q.L."xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/author"Himes B.E."xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/author"Klanderman B."xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/author"Lima J.J."xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/author"Peters S.P."xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/author"Bleecker E.R."xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/author"Hanrahan J.P."xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/author"Irvin C.G."xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/author"Gaume B.R."xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/name"Am J Respir Crit Care Med"xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/pages"449-454"xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/title"Regulatory haplotypes in ARG1 are associated with altered bronchodilator response."xsd:string
http://purl.uniprot.org/citations/20851928http://purl.uniprot.org/core/volume"183"xsd:string
http://purl.uniprot.org/citations/20851928http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20851928
http://purl.uniprot.org/citations/20851928http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20851928
http://purl.uniprot.org/uniprot/#_P05089-mappedCitation-20851928http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20851928
▶