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Coffee, Caffeine and Cardiovascular Disease. Ahmed El-Sohemy. Canada Research Chair in Nutrigenomics. Department of Nutritional Sciences University of Toronto. Nutrigenomics:. Using genomic information and techniques in molecular genetics & genomics to address
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Coffee, Caffeine and Cardiovascular Disease Ahmed El-Sohemy Canada Research Chair in Nutrigenomics Department of Nutritional Sciences University of Toronto
Nutrigenomics: Using genomic information and techniques in molecular genetics & genomics to address issues important to nutrition and health. Diet Genes Food preferences
Why bother with genetics/genomics? Challenges for Nutritional Epidemiology Measurement error Confounding (residual) Recall Bias (case-control)
Is Coffee associated with CVD? Risk No Effect Risk
Is Coffee associated with CVD? • Coffee or associated lifestyle? • Are coffee abstainers at risk? • Does risk depend on age? • Which component of coffee?
Bioactives in coffee aliphatic acids magnesium potassium caffeine caffeine melanoidins diterpenoids polyphenols
SNPs SNPs Caffeine Metabolism Caffeine Target CVD Coffee
SNPs SNPs Caffeine Metabolism Caffeine Target CVD Coffee
Caffeine 1,7-dimethyluric acid 5-acetylamino-6-formylamino-3-methyluracil 1-methylxanthine 1-methyluric acid CYP1A2 Paraxanthine
Genetic Variation in CYP1A2 -163 AC fast slow
Costa Rica Study • 2013 cases (myocardial infarction) • 2013 population-based controls - matched (age, sex, area of residence) • Data collection: - food frequency questionnaire - health and lifestyle questionnaire - fasting blood sample (DNA)
CYP1A2 Genotype Distribution rapid slow
Coffee Intake and Risk of Myocardial Infarction * *P<0.05 Cornelis et al., JAMA 295: 1135-41, 2006
Coffee Intake and Risk of Myocardial Infarction * * A/A A/C + C/C *P<0.05 Cornelis et al., JAMA 295: 1135-41, 2006
Coffee Intake and Risk of Myocardial Infarction Subjects <50 Years of Age * * * * A/A A/C + C/C *P<0.05 Cornelis et al., JAMA 295: 1135-41, 2006
Personalized Dietary Advice vs Public Health Recommendations
Recommended Maximum Caffeine Intake (Health Canada)
Genetic modifiers of exposure Genetic modifiers of biological effect CYP1A2 FMO CYP2A6 NAT2 CYP2E1 UGT SULT CYP1A2 CYP3A4 CYP2D6 CYP1A1 UGT SULT CYP2C9 CYP2E1 UGT GST SULT ADR ADORA HTT GRK HTR COMT CETP PLTP LDLR ACAT SREBP GST ACE TNF NFkB VCAM1 PKC PPARG PDE CREB GLUT PKA GLP1R GLUT FAS1 ACE NOX G6PT1 Caffeine Diterpenes CHD Risk Flavonoids Polyphenols Curr. Opin. Lipidol, 18: 13-19, 2007
Health Outcome Coffee Genotype A Increase Genotype B No effect Genes Genotype C Decrease
Caffeine Consumption Habits Study • Healthy Men and Women aged 20-29 years (n=940) • Food Frequency Questionnaire • Caffeine consumption • Caffeine Consumption Habits Questionnaire • - Acute effects of caffeine • - Caffeine withdrawal symptoms • - Limiting or avoiding caffeine
DRD2 C957T Genotype and “Elevated Mood” Among Men and Women ** * *P<0.05 **P<0.005
DRD2 C957T Genotype and Caffeine Intake Among Men and Women * *P<0.05
ACKNOWLEDGMENTS Hannia Campos Edmond Kabagambe Tom Wolever CCD Investigators Paul Corey David Jenkins Hyeon-Joo Lee Lindsay Stewart Daiva Nielsen Alejandra Navarro-Allende Susana Huang Sarah Herd Darren Brenner Bibiana Garcia-Bailo Marilyn Cornelis Leah Cahill Karen Eny Bénédicte Fontaine-Bisson Ilana Platt Stephen Ozsungur Clare Toguri Advanced Foods and Materials Network Centres of Excellence Natural Sciences and Engineering Research Council Canadian Institutes of Health Research Canada Research Chairs