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A polymorphism in the thyroid hormone receptor gene is associated with bronchodilator response in asthmatics.


ABSTRACT: A pro-asthmatic culture milieu and ?2-agonist (isoproterenol) were previously shown to regulate the expression of select transcription factors (TFs) within human airway epithelial and smooth muscle cells. This study tests 1116 single-nucleotide polymorphisms (SNPs) across 98 of these TF genes for association with bronchodilator response (BDR) in asthma patients. Genotyping was conducted using the Illumina HumanHap550v3 Beadchip in 403 non-Hispanic White asthmatic children and their parents. SNPs were evaluated for association with BDR using family and population-based analyses. Forty-two SNPs providing P-values <0.1 in both analyses were then genotyped in three adult asthma trials. One SNP 5' of the thyroid hormone receptor-? gene was associated with BDR in the childhood population and two adult populations (P-value=0.0012). This investigation identified a novel locus for inter-individual variability in BDR and represents a translation of a cellular drug-response study to potential personalization of clinical asthma management.

SUBMITTER: Duan QL 

PROVIDER: S-EPMC3349771 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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A polymorphism in the thyroid hormone receptor gene is associated with bronchodilator response in asthmatics.

Duan Q L QL   Du R R   Lasky-Su J J   Klanderman B J BJ   Partch A B AB   Peters S P SP   Irvin C G CG   Hanrahan J P JP   Lima J J JJ   Blake K V KV   Liggett S B SB   Litonjua A A AA   Tantisira K G KG  

The pharmacogenomics journal 20120103 2


A pro-asthmatic culture milieu and β2-agonist (isoproterenol) were previously shown to regulate the expression of select transcription factors (TFs) within human airway epithelial and smooth muscle cells. This study tests 1116 single-nucleotide polymorphisms (SNPs) across 98 of these TF genes for association with bronchodilator response (BDR) in asthma patients. Genotyping was conducted using the Illumina HumanHap550v3 Beadchip in 403 non-Hispanic White asthmatic children and their parents. SNPs  ...[more]

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