Gay Caryl L, Zak Rochelle S, Lerdal Anners, Pullinger Clive R, Aouizerat Bradley E, Lee Kathryn A
Department of Family Health Care Nursing, University of California, San Francisco, CA, USA; Department of Research, Lovisenberg Diakonale Hospital, Oslo, Norway; Lovisenberg Diakonale University College, Oslo, Norway.
Sleep Disorders Center, University of California, San Francisco, CA, USA.
Brain Behav Immun. 2015 Jul;47:58-65. doi: 10.1016/j.bbi.2014.11.018. Epub 2014 Dec 20.
Sleep disturbance has been associated with inflammation and cytokine activity, and we previously described genetic associations between cytokine polymorphisms and sleep maintenance and duration among adults with HIV/AIDS. Although sleep onset insomnia (SOI) is also a commonly reported sleep problem, associations between cytokine biomarkers and SOI have not been adequately studied. The purpose of this study was to describe SOI in relation to cytokine plasma concentrations and gene polymorphisms in a convenience sample of 307 adults (212 men, 72 women, and 23 transgender) living with HIV/AIDS. Based on the Pittsburgh Sleep Quality Index item that asks the time it usually took to fall asleep in the past month, participants were categorized as either >30min to fall asleep (n=70, 23%) or 30min or less to fall asleep (n=237). Plasma cytokines were analyzed, and genotyping was conducted for 15 candidate genes involved in cytokine signaling: interferon-gamma (IFNG), IFNG receptor 1 (IFNGR1), interleukins (IL1R2, IL2, IL4, IL6, IL8, IL10, IL13, IL17A), nuclear factor of kappa light polypeptide gene enhancer in B cells (NFKB1 and NFKB2), and tumor necrosis factor alpha (TNFA). Demographic and clinical variables were evaluated as potential covariates. After adjusting for genomic estimates of ancestry, self-reported race/ethnicity and viral load, SOI was associated with higher IL-13 plasma levels and with six single nucleotide polymorphisms (SNPs): IL1B rs1143642 and rs1143623, IL6 rs4719714, IL13 rs1295686, NFKB1 rs4648110, and TNFA rs2857602. In addition, the IL1B rs1143642 polymorphism was associated with plasma levels of IL-1β in adjusted analyses. This study strengthens the evidence for an association between inflammation and sleep disturbance, particularly self-report of habitual SOI. In this chronic illness population, the cytokine polymorphisms associated with SOI provide direction for future personalized medicine intervention research.
睡眠障碍与炎症和细胞因子活性有关，我们之前描述了细胞因子多态性与成人艾滋病毒/艾滋病患者睡眠维持和时长之间的基因关联。尽管入睡失眠（SOI）也是常见的睡眠问题，但细胞因子生物标志物与SOI之间的关联尚未得到充分研究。本研究的目的是在一个由307名艾滋病毒/艾滋病成人（212名男性、72名女性和23名跨性别者）组成的便利样本中，描述与细胞因子血浆浓度和基因多态性相关的SOI情况。根据匹兹堡睡眠质量指数中询问过去一个月通常入睡所需时间的项目，参与者被分为入睡时间>30分钟（n = 70，23%）或入睡时间为30分钟或更短（n = 237）。分析了血浆细胞因子，并对参与细胞因子信号传导的15个候选基因进行了基因分型：干扰素-γ（IFNG）、IFNG受体1（IFNGR1）、白细胞介素（IL1R2、IL2、IL4、IL6、IL8、IL10、IL13、IL17A）、B细胞中κ轻链多肽基因增强子的核因子（NFKB1和NFKB2）以及肿瘤坏死因子α（TNFA）。将人口统计学和临床变量作为潜在协变量进行评估。在调整了祖先的基因组估计值、自我报告的种族/族裔和病毒载量后，SOI与较高的IL-13血浆水平以及六个单核苷酸多态性（SNP）相关：IL1B rs1143642和rs1143623、IL6 rs4719714、IL13 rs1295686、NFKB1 rs4648110和TNFA rs2857602。此外，在调整分析中，IL1B rs1143642多态性与IL-1β的血浆水平相关。本研究强化了炎症与睡眠障碍之间存在关联的证据，尤其是习惯性SOI的自我报告。在这个慢性病群体中，与SOI相关的细胞因子多态性为未来的个性化医学干预研究提供了方向。
