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

Abstract

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 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-β 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.

Figure 1

Odds Ratios (OR) indicate greater likelihood of a high β₂-agonist bronchodilator response for the mutant allele of rs892940 in CAMP, LODO and Sepracor (SEP) trials. Boxes represent the point estimate for each study, the width of which is proportional to the standard error. The summary OR is represented as a diamond, the width of which is proportional to the standard error. Horizontal lines represent 95% confidence intervals.