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Predicting inhaled corticosteroid response in asthma with two associated SNPs

The Pharmacogenomics Journal volume 13, pages 306–311 (2013)Cite this article

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Abstract

Inhaled corticosteroids (ICS) are the most commonly used controller medications prescribed for asthma. Two single-nucleotide polymorphisms (SNPs), rs1876828 in corticotrophin releasing hormone receptor 1 and rs37973 in GLCCI1, have previously been associated with corticosteroid efficacy. We studied data from four existing clinical trials of asthmatics, who received ICS and had lung function measured by forced expiratory volume in 1 s (FEV1) before and after the period of such treatment. We combined the two SNPs rs37973 and rs1876828 into a predictive test of FEV1 change using a Bayesian model, which identified patients with good or poor steroid response (highest or lowest quartile, respectively) with predictive performance of 65.7% (P=0.039 vs random) area under the receiver–operator characteristic curve in the training population and 65.9% (P=0.025 vs random) in the test population. These findings show that two genetic variants can be combined into a predictive test that achieves similar accuracy and superior replicability compared with single SNP predictors.

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Acknowledgements

This work is supported by: U01 HL65899, P01 HL083069, R01 HL092197, K08 HL088046, and T32 HL007427 from the National Heart, Lung and Blood Institute, National Institutes of Health. We thank the participants, investigators, and administrators of the studies considered herein: SOCS/SLIC, LOCCS, and IMPACT. We thank Barbara Klanderman, Trisha Rodgers, and Liz Bevilacqua for their prior effort in genotyping these SNPs at the Channing Lab.

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Authors and Affiliations

  1. Partners Health,

    M J McGeachie, A C Wu, H-H Chang & K G Tantisira

  2. c,

    M J McGeachie, A C Wu, H-H Chang & K G Tantisira

  3. are Center for Personalized Genetic Medicine, Boston, M, A, USA

    M J McGeachie, A C Wu, H-H Chang & K G Tantisira

  4. Department of Medicine, Channing Laboratory, Brigham and Women's Hospital, Boston, M, A, USA

    M J McGeachie, A C Wu & K G Tantisira

  5. Harvard Medical School, Boston, M, A, USA

    M J McGeachie, A C Wu, H-H Chang & K G Tantisira

  6. Harvard-MIT Division of Health Sciences and Technology, Children's Hospital Informatics Program, Boston, M, A, USA

    H-H Chang

  7. Nemours Children's Clinic, Centers for Clinical Pediatric Pharmacology & Pharmacogenetics, Jacksonville, FL, USA

    J J Lima

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

    S P Peters

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  1. M J McGeachie
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Corresponding author

Correspondence to K G Tantisira.

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Competing interests

Dr Peters has served as a consultant for AstraZeneca, Aerocrine, Airsonett AB, Delmedica, GlaxoSmithKline, Merck and TEVA, and is a member of Speakers’ Bureaus sponsored by Integrity Continuing Education and Merck, and is a consultant to the ALA-ACRC's DCC and was PI of its LOCCS trial. Dr Lima has received a $75 000 research grant from Merck. Drs Chang, McGeachie, Peters, Tantisira, and Wu declare no conflict of interest.

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McGeachie, M., Wu, A., Chang, HH. et al. Predicting inhaled corticosteroid response in asthma with two associated SNPs. Pharmacogenomics J 13, 306–311 (2013). https://doi.org/10.1038/tpj.2012.15

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