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Cited by 241Pharmacogenetics and Drug MetabolismCoffee research and impactsGenetic Associations and Epidemiology

The interindividual differences in the 3‐demthylation of caffeine alias CYP1A2 is determined by both genetic and environmental factors

Rasmussen·2002·Pharmacogenetics
DOI 10.1097/00008571-200208000-00008
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Abstract

This study investigated the role of genetic factors (CYP1A2) in caffeine metabolism. The CYP1A2 activity was determined in 378 Danish twins following oral intake of a single dose of 200 mg caffeine and subsequent determination of the caffeine ratio (AFMU+1MU+1MX)/17DMU in a 6-h urine sample. The mean (+/- SD) caffeine ratio was 5.9 +/- 3.4. The caffeine ratio was statistically significantly higher in men compared to women, in smoking men and women compared to non-smoking persons of the same gender and in women not taking oral contraceptives compared with women on oral contraceptives. Thus, we confirmed that CYP1A2 is more active in men than in women, that it is induced by smoking and inhibited by oral contraceptives. In the subsequent analysis of heritability, we included 49 monozygotic twin pairs and 34 same gender dizygotic twin pairs concordant for non-smoking and non-use of oral contraceptives. The intraclass correlation coefficient was 0.798 (95% confidence interval, 0.696-0.900) and 0.394 (95% confidence interval, 0.109-0.680) in the monozygotic and dizygotic twins, respectively. The correlation was statistically significantly higher (P = 0.0015) in the former compared with the latter. A biometrical model for the caffeine ratio including only additive genetic factors and unique environmental factors was the overall best fitting model. Estimates based on this model gave a heritability estimate of 0.725 (95% confidence interval 0.577-0.822). Unique environmental effects seem to account for the remainder 0.275 (95% confidence interval, 0.178-0.423). Our study shows that the CYP1A2 activity is mainly governed by genetic factors.

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Crossref · 10.1097/00008571-200208000-00008

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  • Higher CYP1A2 activity was found in smokers and men than in non-smokers and women, respectively.

    “These authors also found a higher CYP1A2 activity in smokers and men than in non-smokers and women, respectively.”

    From Scientific Opinion on the safety of caffeine (2015) · cites this paper as Rasmussen et al., 2002

  • CYP1A2 polymorphism has been reported to be a source of variability in caffeine metabolism between individuals measured by caffeine metabolites in urine.

    “CYP1A2 polymorphism has been reported to be a source of variability in the metabolism of caffeine between individuals measured by caffeine metabolites in urine (Rasmussen et al., 2002).”

    From Scientific Opinion on the safety of caffeine (2015) · cites this paper as Rasmussen et al., 2002

  • Lower CYP1A2 activity was found in women taking oral contraceptives.

    “A lower CYP1A2 activity was found in women taking oral contraceptives.”

    From Scientific Opinion on the safety of caffeine (2015) · cites this paper as Rasmussen et al., 2002

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Authors
Rasmussen
Venue
Pharmacogenetics
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2002-08-01
Volume
12
Issue
6
Pages
473-478
ISSN
0960-314X (ISSN-L)
DOI
10.1097/00008571-200208000-00008
OpenAlex
W237900477
Cited by
241
References
43
Citations by year
2026: 9 · 2025: 13 · 2024: 8 · 2023: 7 · 2022: 11 · 2021: 8 · 2020: 6 · 2019: 12 · 2018: 11 · 2017: 6 · 2016: 10 · 2015: 9 · 2014: 10 · 2013: 12 · 2012: 13
FWCI
5.89
Type
journal article
Language
en
Open access
closed
Locations
  • Pharmacogenetics (publishedVersion)
  • PubMed (publishedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Health Sciences › Medicine › Pharmacology › Coffee research and impacts
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
caffeine metabolism, CYP1A2, heritability, monozygotic twins, dizygotic twins, smoking, oral contraceptives, sex differences, genetic and environmental factors
MeSH terms
Adolescent, Adult, Central Nervous System Stimulants, Biotransformation, Caffeine, Chromatography, High Pressure Liquid, Contraceptives, Oral, Hormonal, Female, Humans, Male, Middle Aged, Sex Factors, Smoking, Twins, Dizygotic, Twins, Monozygotic, Cytochrome P-450 CYP1A2, Genetic Predisposition to Disease

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