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

A pro-asthmatic culture milieu and beta(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 50 of the thyroid hormone receptor-beta 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. The Pharmacogenomics Journal (2013) 13, 130-136; doi:10.1038/tpj.2011.56; published online 3 January 2012