title: Circadian regulation gene polymorphisms are associated with sleep disruption and duration, and circadian phase and rhythm in adults with HIV.
abstract: Genes involved in circadian regulation, such as circadian locomotor output cycles kaput [CLOCK], cryptochrome [CRY1] and period [PER], have been associated with sleep outcomes in prior animal and human research. However, it is unclear whether polymorphisms in these genes are associated with the sleep disturbances commonly experienced by adults living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Thus, the purpose of this study was to describe polymorphisms in selected circadian genes that are associated with sleep duration or disruption as well as the sleep-wake rhythm strength and phase timing among adults living with HIV/AIDS. A convenience sample of 289 adults with HIV/AIDS was recruited from HIV clinics and community sites in the San Francisco Bay Area. A wrist actigraph was worn for 72 h on weekdays to estimate sleep duration or total sleep time (TST), sleep disruption or percentage of wake after sleep onset (WASO) and several circadian rhythm parameters: mesor, amplitude, the ratio of mesor to amplitude (circadian quotient), and 24-h autocorrelation. Circadian phase measures included clock time for peak activity (acrophase) from actigraphy movement data, and bed time and final wake time from actigraphy and self-report. Genotyping was conducted for polymorphisms in five candidate genes involved in circadian regulation: CLOCK, CRY1, PER1, PER2 and PER3. Demographic and clinical variables were evaluated as potential covariates. Interactions between genotype and HIV variables (i.e. viral load, years since HIV diagnosis) were also evaluated. Controlling for potentially confounding variables (e.g. race, gender, CD4+ T-cell count, waist circumference, medication use, smoking and depressive symptoms), CLOCK was associated with WASO, 24-h autocorrelation and objectively-measured bed time; CRY1 was associated with circadian quotient; PER1 was associated with mesor and self-reported habitual wake time; PER2 was associated with TST, mesor, circadian quotient, 24-h autocorrelation and bed and wake times; PER3 was associated with amplitude, 24-h autocorrelation, acrophase and bed and wake times. Most of the observed associations involved a significant interaction between genotype and HIV. In this chronic illness population, polymorphisms in several circadian genes were associated with measures of sleep disruption and timing. These findings extend the evidence for an association between genetic variability in circadian regulation and sleep outcomes to include the sleep-wake patterns experienced by adults living with HIV/AIDS. These results provide direction for future intervention research related to circadian sleep-wake behavior patterns.
authors.affiliation: a Department of Family Health Care Nursing , University of California at San Francisco , San Francisco , CA , USA .
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Lee
authors.affiliation: a Department of Family Health Care Nursing , University of California at San Francisco , San Francisco , CA , USA .|b Lovisenberg Diakonale Hospital , Oslo , Norway .
authors.forename: Caryl
authors.initials: C
authors.lastname: Gay
authors.affiliation: a Department of Family Health Care Nursing , University of California at San Francisco , San Francisco , CA , USA .
authors.forename: Eeeseung
authors.initials: E
authors.lastname: Byun
authors.affiliation: b Lovisenberg Diakonale Hospital , Oslo , Norway .|c Department of Nursing Science , Faculty of Medicine, Institute of Health and Society, University of Oslo , Oslo , Norway .
authors.forename: Anners
authors.initials: A
authors.lastname: Lerdal
authors.affiliation: d Department of Physiological Nursing .|e Cardiovascular Research Institute , and.
authors.forename: Clive R
authors.initials: CR
authors.lastname: Pullinger
authors.affiliation: d Department of Physiological Nursing .|f Institute for Human Genetics, University of California at San Francisco , San Francisco , CA , USA.
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Aouizerat
mesh_terms: D000204:Activity Cycles / Q000235:genetics*; D000328:Adult; D000368:Aged; D056926:CLOCK Proteins / Q000235:genetics; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics*; D056931:Cryptochromes / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000150:complications* / Q000175:diagnosis; D006184:Habits; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D056950:Period Circadian Proteins / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012495:San Francisco; D012890:Sleep / Q000235:genetics*; D012893:Sleep Wake Disorders / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D013997:Time Factors; D014851:Wakefulness / Q000235:genetics; D055815:Young Adult
chemical_list: C538963:CRY1 protein, human; D056925:Circadian Rhythm Signaling Peptides and Proteins; D056931:Cryptochromes; C539022:PER1 protein, human; C421902:PER2 protein, human; C512644:PER3 protein, human; D056950:Period Circadian Proteins; D056926:CLOCK Proteins; C538943:CLOCK protein, human
keywords: Acrophase; HIV; actigraphy; autocorrelation; chronotype; circadian; genetic; mesor