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

The Pharmacogenomics Journal volume 13, pages 130–136 (2013)Cite this article

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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.

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Acknowledgements

This work was supported by the grants U01 HL65899 and P01 HL083069: The Pharmacogenetics of Asthma Treatment from the National Heart, Lung and Blood Institute (NHLBI). We thank all families for their enthusiastic participation in the CAMP Genetics Ancillary Study, supported by the National Heart, Lung, and Blood Institute, N01-HR-16049. We acknowledge the CAMP investigators and research team for collection of CAMP Genetic Ancillary Study data. Additional support for this research came from Grants N01 HR16044, HR16045, HR16046, HR16047, HR16048, HR16049, HR16050, HR16051 and HR16052 from the National Heart, Lung and Blood Institute. All work on data collected from the CAMP Genetic Ancillary Study was conducted at the Channing Laboratory of the Brigham and Women's Hospital under appropriate CAMP policies and human subject's protections. The CAMP Genetics Ancillary Study is supported by U01 HL075419, U01 HL65899, P01 HL083069, R01 HL086601 and T32 HL07427 Grants from the NHLBI, National Institutes of Health. We acknowledge the American Lung Association (ALA) and the ALA's Asthma Clinical Research Centers investigators and research teams for use of LOCCS and LODO data, with additional funding from HL071394 and HL074755 from the NHLBI, and Nemours Children′s’ Clinic. GlaxoSmithKline supported the conduct of the LOCCS Trial by an unrestricted Grant to the ALA. We acknowledge Sepracor for use of the Sepracor data. QLD receives funding from the Canadian Institutes of Health Research.

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Authors and Affiliations

  1. Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA

    Q L Duan, R Du, J Lasky-Su, B J Klanderman, A B Partch, A A Litonjua & K G Tantisira

  2. Center for Genomics and Personalized Medicine Research, Wake Forest University Health Sciences, Winston-Salem, NC, USA

    S P Peters

  3. Department of Medicine and Physiology, Vermont Lung Center, University of Vermont, Burlington, VT, USA

    C G Irvin

  4. Pulmonary Clinical Research, Sepracor, Marlborough, MA, USA

    J P Hanrahan

  5. Nemours Children's Clinic, Center for Pharmacogenomics and Translational Research, Jacksonville, FL, USA

    J J Lima & K V Blake

  6. Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    S B Liggett

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  1. Q L Duan
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  2. R Du
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  12. A A Litonjua
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Correspondence to Q L Duan.

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Duan, Q., Du, R., Lasky-Su, J. et al. A polymorphism in the thyroid hormone receptor gene is associated with bronchodilator response in asthmatics. Pharmacogenomics J 13, 130–136 (2013). https://doi.org/10.1038/tpj.2011.56

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