Dataset Information

Circulating Interleukin-6 concentration covaries inversely with self-reported sleep duration as a function of polymorphic variation in the glucocorticoid receptor.

ABSTRACT: Growing evidence links extremes of self-reported sleep duration with higher circulating markers of inflammatory disease risk, although not all findings are consistent. Extremes of sleep duration also associate with activation of the hypothalamic-pituitary-adrenocortical (HPA) system and the peripheral release of cortisol, a glucocorticoid (GC) important in downregulating transcription of pro-inflammatory molecules. Polymorphic variation in the gene encoding the GC receptor (GR; NR3C1) modulates cellular sensitivity to GC-mediated anti-inflammatory signaling, thereby affecting levels of pro-inflammatory molecules. Thus, we hypothesized that extremes of self-reported sleep duration may covary with circulating levels of inflammatory markers as a function of allelic variation in NR3C1. Specifically, we examine the possibility that a single nucleotide polymorphism of the GR gene-(rs6198), the minor (G) allele of which confers reduced GR sensitivity-moderates an association of sleep duration with interleukin (IL)-6 and C-reactive protein (CRP) among a large sample (IL-6: N?=?857; CRP: N?=?929) of midlife community volunteers of European ancestry. Findings showed that sleep duration varied inversely with IL-6 (??=?-0.087, p?=?.012), and this association was stronger among individuals homozygous for the rs6198 G-allele compared to alternate genotypes (??=?-0.071, p?=?.039). We also found that sleep duration showed a U-shaped association with CRP (polynomial term: ??=?0.093, p?=?.006), which was not moderated by rs6198 genotype. In conclusion, we show that a common genetic variant in the GR moderates an inverse association of self-reported sleep duration with circulating IL-6, possibly contributing to the increased disease risk observed among some short sleepers.

SUBMITTER: Walsh CP

PROVIDER: S-EPMC6488397 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Circulating Interleukin-6 concentration covaries inversely with self-reported sleep duration as a function of polymorphic variation in the glucocorticoid receptor.

Walsh Catherine P CP Lim Alvin A Marsland Anna L AL Ferrell Robert E RE Manuck Stephen B SB

Brain, behavior, and immunity 20190111

Growing evidence links extremes of self-reported sleep duration with higher circulating markers of inflammatory disease risk, although not all findings are consistent. Extremes of sleep duration also associate with activation of the hypothalamic-pituitary-adrenocortical (HPA) system and the peripheral release of cortisol, a glucocorticoid (GC) important in downregulating transcription of pro-inflammatory molecules. Polymorphic variation in the gene encoding the GC receptor (GR; NR3C1) modulates ...[more]

PMID: 30639698

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Dataset Information

Circulating Interleukin-6 concentration covaries inversely with self-reported sleep duration as a function of polymorphic variation in the glucocorticoid receptor.

Publications

Circulating Interleukin-6 concentration covaries inversely with self-reported sleep duration as a function of polymorphic variation in the glucocorticoid receptor.

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