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Coffee, CYP1A2 Genotype, and Risk of Myocardial Infarction
Open accessAbstract
CONTEXT: The association between coffee intake and risk of myocardial infarction (MI) remains controversial. Coffee is a major source of caffeine, which is metabolized by the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. Individuals who are homozygous for the CYP1A2*1A allele are "rapid" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "slow" caffeine metabolizers. OBJECTIVE: To determine whether CYP1A2 genotype modifies the association between coffee consumption and risk of acute nonfatal MI. DESIGN, SETTING, AND PARTICIPANTS: Cases (n = 2014) with a first acute nonfatal MI and population-based controls (n = 2014) living in Costa Rica between 1994 and 2004, matched for age, sex, and area of residence, were genotyped by restriction fragment-length polymorphism polymerase chain reaction. A food frequency questionnaire was used to assess the intake of caffeinated coffee. MAIN OUTCOME MEASURE: Relative risk of nonfatal MI associated with coffee intake, calculated using unconditional logistic regression. RESULTS: Fifty-five percent of cases (n = 1114) and 54% of controls (n = 1082) were carriers of the slow *1F allele. For carriers of the slow *1F allele, the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of nonfatal MI associated with consuming less than 1, 1, 2 to 3, and 4 or more cups of coffee per day were 1.00 (reference), 0.99 (0.69-1.44), 1.36 (1.01-1.83), and 1.64 (1.14-2.34), respectively. Corresponding ORs (95% CIs) for individuals with the rapid *1A/*1A genotype were 1.00, 0.75 (0.51-1.12), 0.78 (0.56-1.09), and 0.99 (0.66-1.48) (P = .04 for gene x coffee interaction). For individuals younger than the median age of 59 years, the ORs (95% CIs) associated with consuming less than 1, 1, 2 to 3, or 4 or more cups of coffee per day were 1.00, 1.24 (0.71-2.18), 1.67 (1.08-2.60), and 2.33 (1.39-3.89), respectively, among carriers of the *1F allele. The corresponding ORs (95% CIs) for those with the *1A/*1A genotype were 1.00, 0.48 (0.26-0.87), 0.57 (0.35-0.95), and 0.83 (0.46-1.51). CONCLUSION: Intake of coffee was associated with an increased risk of nonfatal MI only among individuals with slow caffeine metabolism, suggesting that caffeine plays a role in this association.
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“The Panel notes that, although this case-control study suggests that polymorphisms of the CYP1A2 gene may affect the risk of MI in relation to caffeine consumption, which may be further affected by polymorphisms of the serotonin receptor gene HTR2A, the results have not yet been replicated and the hypothesis has not been tested in prospective cohort studies.”
From Scientific Opinion on the safety of caffeine (2015) · cites this paper as Cornelis et al., 2006
In the citing paper
“In total, 55 % of cases (n = 1 114) and 54 % of controls (n = 1 082) were carriers of the slow *1F allele, for which the multivariate-adjusted odds ratios (ORs) and 95 % CIs for non-fatal MI associated with the consumption of less than one, one, two to three and four or more cups of coffee per day were 1.00 (reference), 0.99 (0.69-1.44), 1.36 (1.01-1.83)and 1.64 (1.14-2.34),respectively.Cor”
From Scientific Opinion on the safety of caffeine (2015) · cites this paper as Cornelis et al., 2006
In the citing paper
“A study by Cornelis MC et al.47 showed that CYP1A2 genotype was an effect modifier between coffee consumption and risk of myocardial infarction: coffee consumption was related to higher risk of myocardial infarction for the slow caffeine metabolizer, and was not related to myocardial infarction for the fast caffeine metabolizer.”
From Long-Term Coffee Consumption and Risk of Cardiovascular Disease: A Systematic Review and a Dose–Response Meta-Analysis of Prospective Cohort Studies (2014) · cites this paper as [47]
In the citing paper
“However, this analysis was based on a case-control study conducted in Costa Rico and the results have not been replicated in prospective cohort studies yet.”
From Long-Term Coffee Consumption and Risk of Cardiovascular Disease: A Systematic Review and a Dose–Response Meta-Analysis of Prospective Cohort Studies (2014) · cites this paper as [47]
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Nutrigenomics: Hope for Personalized Nutrition
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Personalized Hypertension Management in Practice
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Coffee, CYP1A2 Genotype, and Risk of Myocardial Infarction
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Frequency of Two Genetic Polymorphisms of CYP1A2 Gene in Iranian Population
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“Thus, for efficient drug development, it is essential to identify if the new drug is a substrate, inducer, or inhibitor [4,8-9].”
BackgroundGesundheitsschädigende Wirkungen von Koffein
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POSSIBLE PRODUCTION OF INSTANT COFFEE SUBSTITUTES BASED ON JERUSALEM ARTICHOKE
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Protective Mechanisms and Susceptibility to Xenobiotic Exposure and Load
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Coffee Consumption and Risk of Adverse Outcomes
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Genomic Determinants of Mediterranean Diet Success
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Genomics and Gene-Based Personalized Nutrition
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Effects of Coffee and Caffeine on Mood and Mood Disorders
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“The first example is related to coffee intake, CYP1A2, and myocardial infarction.(22) CYP1A2 is a gene that encodes an enzyme that metabolizes caffeine and exists in 2 forms: a rapid metabolizing and a slow metabolizing form.”
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Metadata
- Authors
- Cornelis, M. C., El-Sohemy, A., Kabagambe, E. K., & Campos, H.
- Affiliations
- University of Toronto (CA)
- Harvard University (US)
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2006-03-08
- Volume
- 295
- Issue
- 10
- Pages
- 1135
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W1972508135
- Cited by
- 490
- References
- 52
- Citations by year
- 2026: 22 · 2025: 26 · 2024: 26 · 2023: 21 · 2022: 20 · 2021: 21 · 2020: 24 · 2019: 24 · 2018: 30 · 2017: 30 · 2016: 21 · 2015: 22 · 2014: 28 · 2013: 22 · 2012: 24
- FWCI
- 16.50
- Type
- journal article
- Language
- en
- Open access
- green
- jamanetwork.com
- Licence
- other-oa
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Investigative News in Education (Universidad de Costa Rica) (submittedVersion)
- Funders
- Harvard University
- Universidad de Costa Rica
- National Heart, Lung, and Blood Institute (HL 60692, HL 071888, R01HL071888, R01HL060692)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Coffee research and impacts
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- coffee consumption, myocardial infarction, caffeine metabolism, gene-environment interaction, cardiovascular risk, Costa Rica, young adults, hormone replacement therapy
- MeSH terms
- Aged, Catchment Area, Health, Coffee, Costa Rica, Female, Genotype, Humans, Male, Middle Aged, Myocardial Infarction, Polymorphism, Restriction Fragment Length, Risk Factors, Logistic Models, Polymerase Chain Reaction, Cytochrome P-450 CYP1A2, Amino Acid Substitution
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