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A Genetic Variation in the Adenosine A 2A Receptor Gene ( ADORA2A ) Contributes to Individual Sensitivity to Caffeine Effects on Sleep
Author(s) -
Rétey J V,
Adam M,
Khatami R,
Luhmann U F O,
Jung H H,
Berger W,
Landolt HP
Publication year - 2007
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100102
Subject(s) - caffeine , adenosine receptor , adenosine , sleep (system call) , stimulant , endocrinology , receptor , pharmacology , medicine , adenosine a2a receptor , psychology , computer science , agonist , operating system
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 A 2A 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 A 2A 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 A 2A receptors for sleep in humans, and suggest that a common variation in ADORA2A contributes to subjective and objective responses to caffeine on sleep. Clinical Pharmacology & Therapeutics (2007) 81 , 692–698. doi: 10.1038/sj.clpt.6100102 ; published online 28 February 2007