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Life stress and diminished expression of genes encoding glucocorticoid receptor and 2-adrenergic receptor in children with asthma
Gregory E. Miller*, and
Edith Chen*
Department of Psychology, University of British Columbia, 2136 West Mall, Vancouver, BC, Canada V6T 1Z4
Edited by Burton H. Singer, Princeton University, Princeton, NJ, and approved January 31, 2006
Received for publication July 25, 2005.
Abstract:
Despite evidence that stressful experience can exacerbate thesymptoms of asthma, little is known about the biological mechanismsthrough which this occurs. This study examined whether lifestress reduces expression of the genes coding for the glucocorticoidreceptor and the 2-adrenergic receptor. A total of 77 childrenwere enrolled in the study (59% male; mean age, 13.5 years).Thirty-nine of them were physician-diagnosed with asthma, and38 were healthy. After an in-depth interview regarding stressfulexperiences, leukocytes were collected through antecubital venipuncture,and real-time RT-PCR was used to quantify mRNA. Chronic stresswas associated with reduced expression of mRNA for the 2-adrenergicreceptor among children with asthma. In the sample of healthychildren, however, the direction of this effect was reversed.The occurrence of a major life event in the 6 months beforethe 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 expressionwas accentuated. Children with asthma who simultaneously experiencedacute and chronic stress exhibited a 5.5-fold reduction in glucocorticoidreceptor mRNA and a 9.5-fold reduction in 2-adrenergic receptormRNA relative to children with asthma without comparable stressorexposure. These findings suggest that stressful experience diminishesexpression of the glucocorticoid and 2-adrenergic receptor genesin children with asthma. To the extent that it diminishes sensitivityto the antiinflammatory properties of glucocorticoids or thebronchodilatory properties of -agonists, this process couldexplain the increased asthma morbidity associated with stress.
Freely available online through the PNAS open access option.
Author contributions: G.E.M. and E.C. designed research; G.E.M.and E.C. analyzed data; and G.E.M. and E.C. wrote the paper.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
*To whom correspondence may be addressed. E-mail: gemiller{at}psych.ubc.ca or echen{at}psych.ubc.ca
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2-adrenergic receptor in children with asthma
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 
