Ahmed El-Sohemy

Department of Nutritional SciencesUniversity of Toronto

Coffee, Caffeine and Cardiovascular Disease

Canada Research Chair in Nutrigenomics

Diet Genes

Nutrigenomics:

Using genomic information and techniques inmolecular genetics & genomics to address issues important to nutrition and health.

Food preferences

Confounding (residual)

Measurement error

Recall Bias (case-control)

Why bother with genetics/genomics?

Challenges for Nutritional Epidemiology

Risk

Risk

No Effect

Is Coffee associated with CVD?

Coffee or associated lifestyle?

Are coffee abstainers at risk?

Does risk depend on age?

Which component of coffee?

Is Coffee associated with CVD?

magnesium

potassium

polyphenols

caffeine

aliphatic acids

diterpenoids

melanoidins

caffeine

Bioactives in coffee

Caffeine (1,3,7-trimethylxanthine)

Coffee CVD

CaffeineMetabolism

SNPs

CaffeineTarget

SNPs

Coffee CVD

CaffeineMetabolism

SNPs

CaffeineTarget

SNPs

Caffeine

CYP1A2

1-methylxanthine

1-methyluric acid

5-acetylamino-6-formylamino-3-methyluracil

1,7-dimethyluric acid

Paraxanthine

CYP1A2 Genotype

A/A A/C C/C

% In

duci

bilit

y

0

50

100

150

200

250

300

Genetic Variation in CYP1A2 -163 AC

slow

fast

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

slow

rapid

CYP1A2

Genotype

Controls

%

Cases

%

A/A

A/C

C/C

46

43

10

45

44

11

Total Population

Od

ds

Ra

tio

0.5

1.0

1.5

2.0

<1 cup/d1 cup/d2-3 cups/d4+ cups/d *

* P<0.05

Coffee Intake and Risk of Myocardial Infarction

Cornelis et al., JAMA 295: 1135-41, 2006

CYP1A2 Genotype

*1A/*1A *1A/*1F + *1F/*1F

Od

ds

Rat

io

0.5

1.0

1.5

2.0

<1 cup/d1 cup/d2-3 cups/d4+ cups/d

A/A A/C + C/C

* P<0.05

*

*

Cornelis et al., JAMA 295: 1135-41, 2006

Coffee Intake and Risk of Myocardial Infarction

CYP1A2 Genotype

*1A/*1A *1A/*1F + *1F/*1F

Od

ds

Rat

io

0

1

2

3

4

<1 cup/d1 cup/d2-3 cups/d4+ cups/d

A/A A/C + C/C

Subjects <50 Years of Age

Coffee Intake and Risk of Myocardial Infarction

* P<0.05

*

*

*

*

Cornelis et al., JAMA 295: 1135-41, 2006

Personalized Dietary Advice

Public Health Recommendations

vs

Adults 10-12 y 7-9 y 4-6 y

Caf

fein

e m

g/d

0

100

200

300

400

500

Pregnant & Nursing

Recommended Maximum Caffeine Intake(Health Canada)

Caffeine

Polyphenols

Diterpenes

ADR ADORAHTT GRKHTR COMT

CETP PLTPLDLR ACATSREBP GST

ACE TNFNFB VCAM1PKC PPARGPDE CREBGLUT PKA

GLP1R GLUTFAS1 ACENOX G6PT1

Genetic modifiersof exposure

Genetic modifiersof biological effect

CHDRisk

Flavonoids

CYP1A2 FMOCYP2A6 NAT2CYP2E1

UGTSULT

CYP1A2 CYP3A4CYP2D6 CYP1A1 UGT SULTCYP2C9 CYP2E1

UGTGSTSULT

Curr. Opin. Lipidol, 18: 13-19, 2007

Increase

Decrease

No effectGenes

Genotype A

Genotype C

Genotype B

HealthOutcomeCoffee

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

Sex

Men Women

% R

epo

rtin

g E

leva

ted

Mo

od

0

10

20

30

40

50

60

70 C/CC/TT/T

* P<0.05

**

*

** P<0.005

DRD2 C957T Genotype and “Elevated Mood” Among Men and Women

Sex

Men Women

Fre

qu

ency

of

TT

Gen

oty

pe

(%)

0

5

10

15

20

25 < 50 mg/d50-200 mg/d> 200 mg/d

* P<0.05

*

DRD2 C957T Genotype and Caffeine Intake Among Men and Women

ACKNOWLEDGMENTS

Marilyn Cornelis Leah CahillKaren Eny Bénédicte Fontaine-Bisson Ilana PlattStephen OzsungurClare Toguri

Canada Research Chairs

Canadian Institutes of Health Research

Natural Sciences and Engineering Research Council

Advanced Foods and Materials Network Centres of Excellence

Hyeon-Joo LeeLindsay Stewart Daiva NielsenAlejandra Navarro-Allende Susana HuangSarah HerdDarren BrennerBibiana Garcia-Bailo

Hannia Campos Edmond KabagambeTom WoleverCCD InvestigatorsPaul CoreyDavid Jenkins