Dataset Information

DQB1*0602 predicts interindividual differences in physiologic sleep, sleepiness, and fatigue.

ABSTRACT:

Objective

The human leukocyte antigen (HLA) DQB1*0602 allele is closely associated with narcolepsy, a neurologic disorder characterized by excessive daytime sleepiness, fragmented sleep, and shortened REM sleep latency. We evaluated whether DQB1*0602 was a novel marker of interindividual differences by determining its relationship to sleep homeostatic, sleepiness, and cognitive responses to baseline and chronic partial sleep deprivation (PSD) conditions.

Methods

Ninety-two DQB1*0602-negative and 37 DQB1*0602-positive healthy adults participated in a protocol of 2 baseline 10 hours time in bed (TIB) nights followed by 5 consecutive 4 hours TIB nights. DQB1*0602 allelic frequencies did not differ significantly between Caucasians and African Americans.

Results

During baseline, although DQB1*0602-positive subjects were subjectively sleepier and more fatigued, they showed greater sleep fragmentation, and decreased sleep homeostatic pressure and differentially sharper declines during the night (measured by non-REM EEG slow-wave energy [SWE]). During PSD, DQB1*0602-positive subjects were sleepier and showed more fragmented sleep, despite SWE elevation comparable to negative subjects. Moreover, they showed differentially greater REM sleep latency reductions and smaller stage 2 reductions, along with differentially greater increases in fatigue. Both groups demonstrated comparable cumulative decreases in cognitive performance.

Conclusions

DQB1*0602 positivity in a healthy population may represent a continuum of some sleep-wake features of narcolepsy. DQB1*0602 was associated with interindividual differences in sleep homeostasis, physiologic sleep, sleepiness, and fatigue-but not in cognitive measures-during baseline and chronic PSD. Thus, DQB1*0602 may represent a genetic biomarker for predicting such individual differences in basal and sleep loss conditions.

SUBMITTER: Goel N

PROVIDER: S-EPMC2974463 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

DQB1*0602 predicts interindividual differences in physiologic sleep, sleepiness, and fatigue.

Goel Namni N Banks Siobhan S Mignot Emmanuel E Dinges David F DF

Neurology 20101001 17

<h4>Objective</h4>The human leukocyte antigen (HLA) DQB1*0602 allele is closely associated with narcolepsy, a neurologic disorder characterized by excessive daytime sleepiness, fragmented sleep, and shortened REM sleep latency. We evaluated whether DQB1*0602 was a novel marker of interindividual differences by determining its relationship to sleep homeostatic, sleepiness, and cognitive responses to baseline and chronic partial sleep deprivation (PSD) conditions.<h4>Methods</h4>Ninety-two DQB1*06 ...[more]

PMID: 20975052

Similar Datasets

Project description:BACKGROUND: Multiple sclerosis (MS) is associated with pathogenic autoimmunity primarily focused on major CNS-myelin target antigens including myelin basic protein (MBP), proteolipidprotein (PLP), myelin oligodendrocyte protein (MOG). MS is a complex trait whereby the HLA genes, particularly class-II genes of HLA-DR15 haplotype, dominate the genetic contribution to disease-risk. Due to strong linkage disequilibrium in HLA-II region, it has been hard to establish precisely whether the functionally relevant effect derives from the DRB1*1501, DQA1*0102-DQB1*0602, or DRB5*0101 loci of HLA-DR15 haplotype, their combinations, or their epistatic interactions. Nevertheless, most genetic studies have indicated DRB1*1501 as a primary risk factor in MS. Here, we used 'HLA-humanized' mice to discern the potential relative contribution of DRB1*1501 and DQB1*0602 alleles to susceptibility to "humanized" MS-like disease induced by PLP, one of the most prominent and encephalitogenic target-antigens implicated in human MS. METHODS: The HLA-DRB1*1501- and HLA-DQB1*0602-Tg mice (MHC-II(-/-)), and control non-HLA-DR15-relevant-Tg mice were immunized with a set of overlapping PLP peptides or with recombinant soluble PLP for induction of "humanized" MS-like disease, as well as for ex-vivo analysis of immunogenic/immunodominant HLA-restricted T-cell epitopes and associated cytokine secretion profile. RESULTS: PLP autoimmunity in both HLA-DR15-Tg mice was focused on 139-151 and 175-194 epitopes. Strikingly, however, the HLA-DRB1*1501-transgenics were refractory to disease induction by any of the overlapping PLP peptides, while HLA-DQB1*0602 transgenics were susceptible to disease induction by PLP139-151 and PLP175-194 peptides. Although both transgenics responded to both peptides, the PLP139-151- and PLP175-194-reactive T-cells were directed to Th1/Th17 phenotype in DQB1*0602-Tg mice and towards Th2 in DRB1*1501-Tg mice. CONCLUSIONS: While genome studies map a strong MS susceptibility effect to the region of DRB1*1501, our findings offer a rationale for potential involvement of pathogenic DQ6-associated autoimmunity in MS. Moreover, that DQB1*0602, but not DRB1*1501, determines disease-susceptibility to PLP in HLA-transgenics, suggests a potential differential, functional role for DQB1*0602 as a predisposing allele in MS. This, together with previously demonstrated disease-susceptibility to MBP and MOG in DRB1*1501-transgenics, also suggests a differential role for DRB1*1501 and DQB1*0602 depending on target antigen and imply a potential complex 'genotype/target antigen/phenotype' relationship in MS heterogeneity.

Project description:BackgroundChildren with attention-deficit/hyperactivity disorder (ADHD) experience greater sleep problems than their peers. Although adolescence is generally a developmental period characterized by insufficient sleep, few studies have used a multi-informant, multi-method design, to examine whether sleep differs in adolescents with and without ADHD.MethodsTargeted recruitment was used to enroll an approximately equal number of eighth-grade adolescents (mean age = 13 years) with (n = 162) and without ADHD (n = 140). Adolescents and parents completed global ratings of sleep problems; adolescents, parents, and teachers completed ratings of daytime sleepiness. Adolescents wore actigraphs and completed a daily sleep diary for approximately 2 weeks.ResultsAdolescents with ADHD were more likely than adolescents without ADHD to obtain insufficient sleep on school days (per diary) and weekends (per diary and actigraphy). Adolescents with ADHD were also more likely to report falling asleep in class and to have stayed up all night at least twice in the previous 2 weeks (14% and 5% reported all-nighters for ADHD and comparison, respectively). In regression analyses controlling for a number of variables known to impact sleep (e.g. pubertal development, sex, medication use, having an externalizing, anxiety, or depression diagnosis), ADHD remained associated with shorter diary and actigraphy school night sleep duration, adolescent- and parent-reported daytime sleepiness, and parent-reported difficulties initiating and maintaining sleep and total sleep disturbance. Controlling for other variables, the odds of being classified with clinically elevated parent-reported sleep disturbance were 6.20 times greater for adolescents with ADHD.ConclusionsFindings provide some of the clearest evidence yet that adolescents with ADHD experience more sleep problems and sleepiness than their peers without ADHD. It may be especially important to assess for sleep problems in adolescents with ADHD and to evaluate whether existing sleep interventions are effective, or can be optimized, for use in adolescents with ADHD who also have sleep problems.

Dataset Information

DQB1*0602 predicts interindividual differences in physiologic sleep, sleepiness, and fatigue.

Objective

Methods

Results

Conclusions

Publications

DQB1*0602 predicts interindividual differences in physiologic sleep, sleepiness, and fatigue.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets