title: Cytokine polymorphisms and plasma levels are associated with sleep onset insomnia in adults living with HIV/AIDS.
abstract: 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.
authors.affiliation: 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.
authors.forename: Caryl L
authors.initials: CL
authors.lastname: Gay
authors.affiliation: Sleep Disorders Center, University of California, San Francisco, CA, USA.
authors.forename: Rochelle S
authors.initials: RS
authors.lastname: Zak
authors.affiliation: Department of Research, Lovisenberg Diakonale Hospital, Oslo, Norway; Department of Nursing Science, Institute of Health and Society, Faculty of Medicine, University of Oslo, Norway.
authors.forename: Anners
authors.initials: A
authors.lastname: Lerdal
authors.affiliation: Department of Physiological Nursing, University of California, San Francisco, CA, USA; Cardiovascular Research Institute, University of California, San Francisco, CA, USA.
authors.forename: Clive R
authors.initials: CR
authors.lastname: Pullinger
authors.affiliation: Department of Physiological Nursing, University of California, San Francisco, CA, USA; Institute for Human Genetics, University of California, San Francisco, CA, USA.
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Aouizerat
authors.affiliation: Department of Family Health Care Nursing, University of California, San Francisco, CA, USA. Electronic address: Kathryn.lee@nursing.ucsf.edu.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Lee
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000328:Adult; D000368:Aged; D016207:Cytokines / Q000097:blood* / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012890:Sleep / Q000235:genetics; D007319:Sleep Initiation and Maintenance Disorders / Q000097:blood / Q000150:complications / Q000235:genetics*; D055815:Young Adult
chemical_list: D016207:Cytokines
keywords: Biomarker; Cytokine; Genetic; HIV; Inflammation; Insomnia; Sleep onset latency