The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Genomewide Association between GLCCI1 and Response to Glucocorticoid Therapy in Asthma
Open accessAbstract
BACKGROUND: The response to treatment for asthma is characterized by wide interindividual variability, with a significant number of patients who have no response. We hypothesized that a genomewide association study would reveal novel pharmacogenetic determinants of the response to inhaled glucocorticoids. METHODS: We analyzed a small number of statistically powerful variants selected on the basis of a family-based screening algorithm from among 534,290 single-nucleotide polymorphisms (SNPs) to determine changes in lung function in response to inhaled glucocorticoids. A significant, replicated association was found, and we characterized its functional effects. RESULTS: We identified a significant pharmacogenetic association at SNP rs37972, replicated in four independent populations totaling 935 persons (P=0.0007), which maps to the glucocorticoid-induced transcript 1 gene (GLCCI1) and is in complete linkage disequilibrium (i.e., perfectly correlated) with rs37973. Both rs37972 and rs37973 are associated with decrements in GLCCI1 expression. In isolated cell systems, the rs37973 variant is associated with significantly decreased luciferase reporter activity. Pooled data from treatment trials indicate reduced lung function in response to inhaled glucocorticoids in subjects with the variant allele (P=0.0007 for pooled data). Overall, the mean (±SE) increase in forced expiratory volume in 1 second in the treated subjects who were homozygous for the mutant rs37973 allele was only about one third of that seen in similarly treated subjects who were homozygous for the wild-type allele (3.2±1.6% vs. 9.4±1.1%), and their risk of a poor response was significantly higher (odds ratio, 2.36; 95% confidence interval, 1.27 to 4.41), with genotype accounting for about 6.6% of overall inhaled glucocorticoid response variability. CONCLUSIONS: A functional GLCCI1 variant is associated with substantial decrements in the response to inhaled glucocorticoids in patients with asthma.
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Cites
A haplotype map of the human genome
The International HapMap Consortium (2005) · Nature · doi:10.1038/nature04226 · Cited by 5,858
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Long-Term Effects of Budesonide or Nedocromil in Children with Asthma
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Population genomics of human gene expression
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A common genetic variant is associated with adult and childhood obesity.
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Significant variability in response to inhaled corticosteroids for persistent asthma
Szefler, S. J., Martin, R. J., King, T. S., Boushey, H. A., Cherniack, R. M., Chinchilli, V. M., Craig, T. J., Dolovich, M., Drazen, J. M., Fagan, J. K., et al. (2002) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2002.122635 · Cited by 622
Self-citationIsrael, E., Chinchilli, V. M., Ford, J. G., Boushey, H. A., Cherniack, R., Craig, T. J., Deykin, A., Fagan, J. K., Fahy, J. V., Fish, J., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17273-5 · Cited by 602
Self-citationCharacterization of within-subject responses to fluticasone and montelukast in childhood asthma
Szefler, S. J., Phillips, B. R., Martinez, F. D., Chinchilli, V. M., Lemanske, R. F., Strunk, R. C., Zeiger, R. S., Larsen, G., Spahn, J. D., Bacharier, L. B., et al. (2005) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2004.11.014 · Cited by 586
Self-citationDrazen, J. M., Yandava, C. N., Dubé, L., Szczerback, N., Hippensteel, R., Pillari, A., Israel, E., Schork, N., Silverman, E. S., Katz, D. A., et al. (1999) · Nature Genetics · doi:10.1038/9680 · Cited by 560
Cited by
International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma
Chung, K. F., Wenzel, S. E., Brozek, J. L., Bush, A., Castro, M., Sterk, P. J., Adcock, I. M., Bateman, E. D., Bel, E. H., Bleecker, E. R., et al. (2014) · European Respiratory Journal · doi:10.1183/09031936.00202013 · Cited by 3,926
Clinical Pharmacology of Corticosteroids
Williams, D. M. (2018) · Respiratory Care · doi:10.4187/respcare.06314 · Cited by 460
Glucocorticoid sensitivity in health and disease
Quax, R. A., Manenschijn, L., Koper, J. W., Hazes, J. M., Lamberts, S. W. J., van Rossum, E. F. C., & Feelders, R. A. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.183 · Cited by 310
Ortega, V. E., & Meyers, D. A. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.10.040 · Cited by 237
Glucocorticoids and the regulation of growth hormone secretion
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Metadata
- Authors
- Tantisira, K. G., Lasky-Su, J., Harada, M., Murphy, A., Litonjua, A. A., Himes, B. E., Lange, C., Lazarus, R., Sylvia, J., Klanderman, B., Duan, Q. L., Qiu, W., Hirota, T., Martinez, F. D., Mauger, D., Sorkness, C., Szefler, S., Lazarus, S. C., Lemanske, R. F., Peters, S. P., Lima, J. J., Nakamura, Y., Tamari, M., & Weiss, S. T.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2011-09-29
- Volume
- 365
- Issue
- 13
- Pages
- 1173-1183
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2009540187
- Cited by
- 366
- References
- 38
- FWCI
- 24.46
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Tantisira, K. G., Lasky-Su, J., Harada, M., Murphy, A., Litonjua, A. A., Himes, B. E., Lange, C., Lazarus, R., Sylvia, J., Klanderman, B., Duan, Q. L., Qiu, W., Hirota, T., Martinez, F. D., Mauger, D., Sorkness, C., Szefler, S., Lazarus, S. C., Lemanske, R. F., . . . Weiss, S. T. (2011). Genomewide Association between GLCCI1 and Response to Glucocorticoid Therapy in Asthma. New England Journal of Medicine. https://doi.org/10.1056/nejmoa0911353
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
