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Cited by 200Asthma and respiratory diseasesStress Responses and CortisolAdrenal Hormones and Disorders

Life stress and diminished expression of genes encoding glucocorticoid receptor and β 2 -adrenergic receptor in children with asthma

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Miller, Gregory E., Chen, Edith·2006·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0506312103PMC PMC1414639
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Abstract

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 been found in several other disorders including anxiety, posttraumatic stress disorder, asthma, rheumatoid arthritis, cardiovascular disease, inflammatory bowel disease, autoimmune diseases, and some cancers.

    “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

    The Abstract reports reduced glucocorticoid-receptor mRNA in children with asthma exposed to both acute and chronic stress. The Discussion says this could diminish glucocorticoid sensitivity, but sensitivity was not measured directly. The paper does not address the other listed disorders. (LLM, conf=0.88)

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1 of the 40 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. [21]Gao H., Xue Q., Lin Y., Wang L., Zhu G., Zhao Q., Chen Y. Chin. Med. J. 2001;114:1317–1319. [PubMed] [Google Scholar]
  2. [24]Mills P. J., Adler K. A., Dimsdale J. E., Perez C. J., Ziegler M. G., Ancoli-Israel S., Patterson T. L., Grant I. Am. J. Geriatr. Psychiatry. 2004;12:281–286. [PubMed] [Google Scholar]
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Authors
Miller, G. E., & Chen, E.
Affiliations
University of British Columbia (CA)
ORCID
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
DOI
10.1073/pnas.0506312103
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
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 › Physiology › 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

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