Cited by 278Coffee research and impactsSleep and related disordersSleep and Wakefulness Research

A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep

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Rétey, J V, Adam, M, Khatami, R, Luhmann, U F O, Jung, H H, Berger, W, Landolt, H-P·2007·Clinical Pharmacology & Therapeutics

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.

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Crossref · 10.1038/sj.clpt.6100102

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  • Variation in the expression of genes such as CYP1A2 and ADORA2A are suggested to modulate the rate of metabolism and sensitivity.

    “Variation in the expression of genes such as cytochrome P450 1A2 (CYP1A2) [91] and adenosine A2A receptor (ADORA2A) [92] are suggested to modulate the rate of metabolism and sensitivity.”
  • Common variants of the gene encoding for the A2a receptor can disrupt sleep or cause anxiety in some individuals after ingesting caffeine.

    “For example, common variants of the gene encoding for the A2a receptor can disrupt sleep (51) or cause anxiety in some individuals (52) after ingesting caffeine.”

    From The Safety of Ingested Caffeine: A Comprehensive Review (2017) · cites this paper as [51]

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Authors
Rétey, J. V., Adam, M., Khatami, R., Luhmann, U. F. O., Jung, H. H., Berger, W., & Landolt, H.-P.
Affiliations
  • University of Zurich (CH)
  • University Hospital Zurich (CH)
Corresponding author
Landolt, H-P
Venue
Clinical Pharmacology & Therapeutics
Publisher
Wiley
Published
2007-02-28
Volume
81
Issue
5
Pages
692-698
ISSN
  • 0009-9236 (ISSN-L)
  • 1532-6535
OpenAlex
W2035474281
Cited by
278
References
48
Citations by year
2026: 11 · 2025: 11 · 2024: 12 · 2023: 14 · 2022: 8 · 2021: 12 · 2020: 22 · 2019: 17 · 2018: 13 · 2017: 13 · 2016: 16 · 2015: 17 · 2014: 14 · 2013: 10 · 2012: 26
FWCI
9.75
Type
journal article
Language
en
Open access
Locations
  • Clinical Pharmacology & Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Topics
  • Health Sciences › Medicine › Pharmacology › Coffee research and impacts
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Keywords
caffeine, adenosine A2A receptor, caffeine sensitivity, sleep quality, genetic variation, insomnia, habitual caffeine consumption
MeSH terms
Adult, Aged, Alleles, Central Nervous System Stimulants, Caffeine, Data Interpretation, Statistical, DNA, Electroencephalography, Female, Genotype, Humans, Male, Middle Aged, Surveys and Questionnaires, Sleep, Genetic Variation, Polysomnography, Reverse Transcriptase Polymerase Chain Reaction, Internet, Receptor, Adenosine A2A

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