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Sleep disturbances and inflammatory gene expression among pregnant women: Differential responses by race
Judith E Carroll1, Kelly E Rentscher1, Steven W Cole1
1Cousins Center for Psychoneuroimmunology, Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA.
Excessive inflammation in pregnancy predicts adverse birth outcomes, including shortened gestational length and lower birthweight, with African American women at greater risk. As substantial racial disparities in sleep quality, and evidence that African Americans have increased vulnerability for sleep-induced inflammatory dysregulation, sleep may be a critical, modifiable health behavior that contributes to racial disparities in birth outcomes. The present study examined sleep disturbance as a predictor of genome-wide transcriptome profiles of peripheral blood samples from 103 pregnant women (33 African American, 70 white) assessed at 18.7 ± 7.2 weeks gestation. We hypothesized that pregnant women with significant sleep disturbances would have gene expression profiles indicating over-expression of inflammatory pathways, with greater effects among African American compared to white women. Promoter-based bioinformatics analyses of differentially expressed genes indicated greater activation of NF-кB, AP1, and CREB transcription factors among African American women with sleep disturbances (all p < 0.05), and enhanced activation of AP1, but not NF-кB and reduced CREB activity among white women with sleep disturbances (p < 0.05). Differences in glucocorticoid receptor (GR) activity were also observed, in which African American women with sleep disturbances had reduced GR activity (p < 0.05), but white women with sleep disturbances showed a trend for enhanced GR activity (p = 0.11). Similarly, Interferon Response Factor (IRF) activity was reduced in African American women while increased in white women with sleep disturbances (p < 0.05). The current study provides novel evidence for gene expression related to inflammation, glucocorticoids, and anti-viral immunity among pregnant women with sleep disturbances, with differential effects by race. African Americans showed greater breadth and magnitude in these proinflammatory and anti-viral pathways than whites, with divergence in anti-inflammatory glucocorticoid, proinflammatory adrenergic-mediated cAMP, and anti-viral interferon responses. These data elucidate the role of sleep disturbances in intracellular inflammatory and anti-viral immunity in pregnancy and provide a potential target for intervention.
Excessive inflammation in pregnancy predicts adverse birth outcomes, including shortened gestational length and lower birthweight, with African American women at greater risk. As substantial racial disparities in sleep quality, and evidence that African Americans have increased vulnerability for sleep-induced inflammatory dysregulation, sleep may be a critical, modifiable health behavior that contributes to racial disparities in birth outcomes. The present study examined sleep disturbance as a predictor of genome-wide transcriptome profiles of peripheral blood samples from 103 pregnant women (33 African American, 70 white) assessed at 18.7 ± 7.2 weeks gestation. We hypothesized that pregnant women with significant sleep disturbances would have gene expression profiles indicating over-expression of inflammatory pathways, with greater effects among African American compared to white women. Promoter-based bioinformatics analyses of differentially expressed genes indicated greater activation of NF-кB, AP1, and CREB transcription factors among African American women with sleep disturbances (all p < 0.05), and enhanced activation of AP1, but not NF-кB and reduced CREB activity among white women with sleep disturbances (p < 0.05). Differences in glucocorticoid receptor (GR) activity were also observed, in which African American women with sleep disturbances had reduced GR activity (p < 0.05), but white women with sleep disturbances showed a trend for enhanced GR activity (p = 0.11). Similarly, Interferon Response Factor (IRF) activity was reduced in African American women while increased in white women with sleep disturbances (p < 0.05). The current study provides novel evidence for gene expression related to inflammation, glucocorticoids, and anti-viral immunity among pregnant women with sleep disturbances, with differential effects by race. African Americans showed greater breadth and magnitude in these proinflammatory and anti-viral pathways than whites, with divergence in anti-inflammatory glucocorticoid, proinflammatory adrenergic-mediated cAMP, and anti-viral interferon responses. These data elucidate the role of sleep disturbances in intracellular inflammatory and anti-viral immunity in pregnancy and provide a potential target for intervention.
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