Department of Psychology, University of Pittsburgh, United States.
Department of Psychology, University of Pittsburgh, United States.
Brain Behav Immun. 2019 May;78:21-30. doi: 10.1016/j.bbi.2019.01.002. Epub 2019 Jan 11.
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 (β = -0.087, p = .012), and this association was stronger among individuals homozygous for the rs6198 G-allele compared to alternate genotypes (β = -0.071, p = .039). We also found that sleep duration showed a U-shaped association with CRP (polynomial term: β = 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.
越来越多的证据表明，自我报告的睡眠时间过长或过短与循环炎症标志物的风险增加有关，但并非所有研究结果都一致。睡眠时间过长或过短还与下丘脑-垂体-肾上腺皮质（HPA）系统的激活和皮质醇的外周释放有关，皮质醇是一种糖皮质激素（GC），对下调促炎分子的转录至关重要。编码 GC 受体（GR；NR3C1）的基因多态性改变调节细胞对 GC 介导的抗炎信号的敏感性，从而影响促炎分子的水平。因此，我们假设自我报告的睡眠时间过长或过短可能与循环炎症标志物水平相关，这是 NR3C1 等位基因变异的函数。具体来说，我们研究了 GR 基因单核苷酸多态性（rs6198）的可能性，其次要等位基因（G）赋予了降低的 GR 敏感性，这种等位基因是否可以调节睡眠持续时间与白细胞介素（IL）-6 和 C 反应蛋白（CRP）之间的关联，这是一项在欧洲血统的中年社区志愿者的大样本（IL-6：N=857；CRP：N=929）中进行的研究。研究结果表明，睡眠时间与 IL-6 呈负相关（β=-0.087，p=0.012），而在 rs6198 G 等位基因纯合子个体中，这种关联比其他基因型更强（β=-0.071，p=0.039）。我们还发现，睡眠时间与 CRP 呈 U 型关联（多项式项：β=0.093，p=0.006），而 rs6198 基因型不能调节这种关联。总之，我们的研究结果表明，GR 中的常见遗传变异调节了自我报告的睡眠时间与循环 IL-6 之间的负相关关系，这可能导致一些睡眠不足者的疾病风险增加。
