DQB1*0602 predicts interindividual differences in physiologic sleep, sleepiness, and fatigue.
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.
Goel
Namni
N
Division of Sleep and Chronobiology, Unit for Experimental Psychiatry, Department of Psychiatry, University of Pennsylvania School of Medicine, 1013 Blockley Hall, Philadelphia, PA 19104-6021, USA. goel@mail.med.upenn.edu
Banks
Siobhan
S
Mignot
Emmanuel
E
Dinges
David F
DF
D000328:Adult; D000704:Analysis of Variance; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics; D004569:Electroencephalography / Q000379:methods; D056344:Executive Function / Q000502:physiology; D005221:Fatigue / Q000150:complications / Q000235:genetics*; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006801:Humans; D007206:Individuality; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D009483:Neuropsychological Tests; D017286:Polysomnography / Q000379:methods; D012890:Sleep / Q000235:genetics*; D007319:Sleep Initiation and Maintenance Disorders / Q000150:complications / Q000235:genetics*; D055815:Young Adult
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D008562:Membrane Glycoproteins