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Life stress and diminished expression of genes encoding glucocorticoid receptor and β 2 -adrenergic receptor in children with asthma
Open accessAbstract
Despite evidence that stressful experience can exacerbate the symptoms of asthma, little is known about the biological mechanisms through which this occurs. This study examined whether life stress reduces expression of the genes coding for the glucocorticoid receptor and the β 2 -adrenergic receptor. A total of 77 children were enrolled in the study (59% male; mean age, 13.5 years). Thirty-nine of them were physician-diagnosed with asthma, and 38 were healthy. After an in-depth interview regarding stressful experiences, leukocytes were collected through antecubital venipuncture, and real-time RT-PCR was used to quantify mRNA. Chronic stress was associated with reduced expression of mRNA for the β 2 -adrenergic receptor among children with asthma. In the sample of healthy children, however, the direction of this effect was reversed. The occurrence of a major life event in the 6 months before the study was not sufficient to influence patterns of gene expression. When such events occurred in the context of a chronic stressor, however, their association with patterns of gene expression was accentuated. Children with asthma who simultaneously experienced acute and chronic stress exhibited a 5.5-fold reduction in glucocorticoid receptor mRNA and a 9.5-fold reduction in β 2 -adrenergic receptor mRNA relative to children with asthma without comparable stressor exposure. These findings suggest that stressful experience diminishes expression of the glucocorticoid and β 2 -adrenergic receptor genes in children with asthma. To the extent that it diminishes sensitivity to the antiinflammatory properties of glucocorticoids or the bronchodilatory properties of β-agonists, this process could explain the increased asthma morbidity associated with stress.
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“Evidence of altered glucocorticoid sensitivity has also been found in several other disorders including anxiety, posttraumatic stress disorder, asthma, rheumatoid arthritis, cardiovascular disease, inflammatory bowel disease, autoimmune diseases, and some cancers”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as G. E. Miller & Chen, 2006
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Metadata
- Authors
- Miller, G. E., & Chen, E.
- Affiliations
- University of British Columbia (CA)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-04-04
- Volume
- 103
- Issue
- 14
- Pages
- 5496-5501
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1414639
- OpenAlex
- W2125433950
- Cited by
- 199
- References
- 40
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 13 · 2023: 7 · 2022: 9 · 2021: 8 · 2020: 12 · 2019: 9 · 2018: 7 · 2017: 9 · 2016: 11 · 2015: 13 · 2014: 10 · 2013: 4 · 2012: 11
- FWCI
- 9.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- William T. Grant Foundation
- Michael Smith Health Research BC
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- childhood asthma, life events, glucocorticoid receptor, beta2-adrenergic receptor, gene expression, chronic stress, major life events, leukocytes, glucocorticoid sensitivity
- MeSH terms
- Adolescent, Asthma, Base Sequence, Child, Female, Humans, Life Change Events, Male, Receptors, Glucocorticoid, Stress, Psychological, Cohort Studies, Gene Expression, DNA Primers, Receptors, Adrenergic, beta-2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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