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A Genetic Variation in the Adenosine A2A Receptor Gene (ADORA2A) Contributes to Individual Sensitivity to Caffeine Effects on Sleep
Open accessAbstract
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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“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.”
From The effect of caffeine on subsequent sleep: A systematic review and meta-analysis (2023) · cites this paper as [92]
In the citing paper
“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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Metadata
- 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
- green
- doi.org
- 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 (medical) › 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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