Caffeine intake and CYP1A2 variants associated with high caffeine intake protect non-smokers from hypertension
Open accessAbstract
The 15q24.1 locus, including CYP1A2, is associated with blood pressure (BP). The CYP1A2 rs762551 C allele is associated with lower CYP1A2 enzyme activity. CYP1A2 metabolizes caffeine and is induced by smoking. The association of caffeine consumption with hypertension remains controversial. We explored the effects of CYP1A2 variants and CYP1A2 enzyme activity on BP, focusing on caffeine as the potential mediator of CYP1A2 effects. Four observational (n = 16 719) and one quasi-experimental studies (n = 106) including European adults were conducted. Outcome measures were BP, caffeine intake, CYP1A2 activity and polymorphisms rs762551, rs1133323 and rs1378942. CYP1A2 variants were associated with hypertension in non-smokers, but not in smokers (CYP1A2-smoking interaction P = 0.01). Odds ratios (95% CIs) for hypertension for rs762551 CC, CA and AA genotypes were 1 (reference), 0.78 (0.59-1.02) and 0.66 (0.50-0.86), respectively, P = 0.004. Results were similar for the other variants. Higher CYP1A2 activity was linearly associated with lower BP after quitting smoking (P = 0.049 and P = 0.02 for systolic and diastolic BP, respectively), but not while smoking. In non-smokers, the CYP1A2 variants were associated with higher reported caffeine intake, which in turn was associated with lower odds of hypertension and lower BP (P = 0.01). In Mendelian randomization analyses using rs1133323 as instrument, each cup of caffeinated beverage was negatively associated with systolic BP [-9.57 (-16.22, -2.91) mmHg]. The associations of CYP1A2 variants with BP were modified by reported caffeine intake. These observational and quasi-experimental results strongly support a causal role of CYP1A2 in BP control via caffeine intake.
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CYP1A2 is a major enzyme responsible for metabolism of caffeine and plays an important role in metabolism of estrogen and coffee.
“CYP1A2 is a major enzyme responsible for the metabolism of purine alkaloid (1,3,7-trimethylxanthine), a caffeine that occurs naturally in coffee beans, and plays an important role in the metabolism of estrogen and coffee [14].”
From Effect of Caffeine Consumption on the Risk for Neurological and Psychiatric Disorders: Sex Differences in Human (2020) · cites this paper as [14]
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Additional file 1 of The association between caffeine intake and testosterone: NHANES 2013–2014
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- Authors
- Guessous, I., Dobrinas, M., Kutalik, Z., Pruijm, M., Ehret, G., Maillard, M., Bergmann, S., Beckmann, J. S., Cusi, D., Rizzi, F., Cappuccio, F., Cornuz, J., Paccaud, F., Mooser, V., Gaspoz, J.-M., Waeber, G., Burnier, M., Vollenweider, P., Eap, C. B., & Bochud, M.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- SIB Swiss Institute of Bioinformatics (CH)
- University of Milan (IT)
- University of Lausanne (CH)
- University of Geneva (CH)
- Corresponding author
- Bochud, Murielle
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-04-05
- Volume
- 21
- Issue
- 14
- Pages
- 3283-3292
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2124427968
- Cited by
- 70
- References
- 64
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 3 · 2021: 7 · 2020: 7 · 2019: 4 · 2018: 8 · 2017: 5 · 2016: 6 · 2015: 5 · 2014: 4 · 2013: 2 · 2012: 2
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- reroDoc Digital Library (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Coffee research and impacts
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- caffeine consumption, CYP1A2, hypertension, blood pressure, rs762551, CYP1A2 polymorphism, smoking, smoking cessation, Mendelian randomization, non-smokers
- MeSH terms
- Adult, Aged, Blood Pressure, Caffeine, Female, Genotype, Humans, Hypertension, Male, Middle Aged, Polymorphism, Genetic, Smoking, Genetic Variation, Cytochrome P-450 CYP1A2, White People
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