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