title: Functional ADA polymorphism increases sleep depth and reduces vigilant attention in humans.
abstract: Homeostatically regulated slow-wave oscillations in non-rapid eye movement (REM) sleep may reflect synaptic changes across the sleep-wake continuum and the restorative function of sleep. The nonsynonymous c.22G>A polymorphism (rs73598374) of adenosine deaminase (ADA) reduces the conversion of adenosine to inosine and predicts baseline differences in sleep slow-wave oscillations. We hypothesized that this polymorphism affects cognitive functions, and investigated whether it modulates electroencephalogram (EEG), behavioral, subjective, and biochemical responses to sleep deprivation. Attention, learning, memory, and executive functioning were quantified in healthy adults. Right-handed carriers of the variant allele (G/A genotype, n = 29) performed worse on the d2 attention task than G/G homozygotes (n = 191). To test whether this difference reflects elevated homeostatic sleep pressure, sleep and sleep EEG before and after sleep deprivation were studied in 2 prospectively matched groups of G/A and G/G genotype subjects. Deep sleep and EEG 0.75- to 1.5-Hz oscillations in non-REM sleep were significantly higher in G/A than in G/G genotype. Moreover, attention and vigor were reduced, whereas waking EEG alpha activity (8.5-12 Hz), sleepiness, fatigue, and α-amylase in saliva were enhanced. These convergent data demonstrate that genetic reduction of ADA activity elevates sleep pressure and plays a key role in sleep and waking quality in humans.
authors: Institute of Pharmacology and Toxicology University of Zurich, Zurich, Switzerland.
authors: Valérie
authors: V
authors: Bachmann
authors: Federica
authors: F
authors: Klaus
authors: Sereina
authors: S
authors: Bodenmann
authors: Nikolaus
authors: N
authors: Schäfer
authors: Peter
authors: P
authors: Brugger
authors: Susanne
authors: S
authors: Huber
authors: Wolfgang
authors: W
authors: Berger
authors: Hans-Peter
authors: HP
authors: Landolt
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D000328:Adult; D000704:Analysis of Variance; D001288:Attention / Q000502:physiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004585:Electrooculography; D056344:Executive Function / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D007858:Learning / Q000502:physiology; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D017286:Polysomnography; D011597:Psychomotor Performance / Q000502:physiology; D012463:Saliva / Q000378:metabolism; D012892:Sleep Deprivation / Q000235:genetics*; D012894:Sleep Stages / Q000235:genetics; D011795:Surveys and Questionnaires; D055815:Young Adult; D000516:alpha-Amylases / Q000378:metabolism
chemical_list: D000516:alpha-Amylases; C548482:ADA protein, human; D000243:Adenosine Deaminase