title: A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep.
abstract: Caffeine is the most widely used stimulant in Western countries. Some people voluntarily reduce caffeine consumption because it impairs the quality of their sleep. Studies in mice revealed that the disruption of sleep after caffeine is mediated by blockade of adenosine A2A receptors. Here we show in humans that (1) habitual caffeine consumption is associated with reduced sleep quality in self-rated caffeine-sensitive individuals, but not in caffeine-insensitive individuals; (2) the distribution of distinct c.1083T>C genotypes of the adenosine A2A receptor gene (ADORA2A) differs between caffeine-sensitive and -insensitive adults; and (3) the ADORA2A c.1083T>C genotype determines how closely the caffeine-induced changes in brain electrical activity during sleep resemble the alterations observed in patients with insomnia. These data demonstrate a role of adenosine A2A receptors for sleep in humans, and suggest that a common variation in ADORA2A contributes to subjective and objective responses to caffeine on sleep.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zürich, and Department of Neurology, University Hospital, Zürich, Switzerland.
authors.forename: J V
authors.initials: JV
authors.lastname: Rétey
authors.forename: M
authors.initials: M
authors.lastname: Adam
authors.forename: R
authors.initials: R
authors.lastname: Khatami
authors.forename: U F O
authors.initials: UF
authors.lastname: Luhmann
authors.forename: H H
authors.initials: HH
authors.lastname: Jung
authors.forename: W
authors.initials: W
authors.lastname: Berger
authors.forename: H-P
authors.initials: HP
authors.lastname: Landolt
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004247:DNA / Q000235:genetics; D003627:Data Interpretation, Statistical; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D020407:Internet; D008297:Male; D008875:Middle Aged; D017286:Polysomnography / Q000187:drug effects; D043705:Receptor, Adenosine A2A / Q000235:genetics* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012890:Sleep / Q000187:drug effects*; D011795:Surveys and Questionnaires
chemical_list: D000697:Central Nervous System Stimulants; D043705:Receptor, Adenosine A2A; D002110:Caffeine; D004247:DNA