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PREHRANA IN ČLOVEŠKI GENOM (NUTRIGENOMIKA in NUTRIGENETIKA) Simon Horvat

Simon Horvat

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Page 1: Simon Horvat

PREHRANA IN ČLOVEŠKI GENOM (NUTRIGENOMIKA in NUTRIGENETIKA)

Simon Horvat

Page 2: Simon Horvat

TODAY’S MENU

•  Definitions •  Nutrigenetics •  Nutrigenomics

– Transcriptome – Proteome – Metabolom – Microbiome

•  Challenges and Outlooks

Level: DNA

RNA PROTEIN METABOLITES MICROBIOTA

Page 3: Simon Horvat

NUTRIGENOMICS How nutrients affect

transcriptome, proteome, Metabolome…

NUTRIGENETICS How gene variants

respond (differentially) to nutrients

Page 4: Simon Horvat

Pérez-Martínez P, Pérez-Jiménez F, Ordovás JM, The APOB -516C/T polymorphism is associated with differences in insulin sensitivity in healthy males during the consumption of diets with different fat content., British Journal of Nutrition 2007 Apr;97(4):622-7

NUTRIGENETICS – case study

SFA: “Western” diet 15% protein, 47% carbohydrate (CHO) 38% fat

MUFA diet 15% protein, 47% carbohydrate (CHO) 38% fat (10% SFA, 6% PUFA 22% MUFA)

CHO diet 15% protein, 55% carbohydrate (CHO) >30% fat

HUMAN TRIAL!

Page 5: Simon Horvat

Fig. 2 Plasma glucose at the end of test following insulin suppresion! At the end of diet trial all people received infusion of somatostatin (inhibits endogenous insulin secretion), insulin and glucose. Plasma glucose values were significantly higher in C/T than in C/C subjects after the MUFA, CHO and SFA diets suggesting that C/T genotype is more insulin resistant.

-516 C/T ApoB genotypes (especially males) were more insulin resistant than -516 C/C genotype after consuming all three diets, effect largest in SFA diet

Plas

ma

gluc

ose

(mm

ol /

l)

NUTRIGENETICS – case study Pérez-Martínez et al : Br J Nutr. 2007:622-7

Main result

-516 C/C

-516 C/T

Page 6: Simon Horvat

NUTRIGENETICS – examples from companies selling nutrigenetic tests

GENOVA DIAGNOSTICS http://www.genovadiagnostics.com

……

Page 7: Simon Horvat

NUTRIGENETICS- GOOD EXAMPLE –Choline SNPs

Big Study - Pregnant women in California -too low choline in 25% women (high correlation to PEMT SNP

--à birth defects (Sha et al 2010; Zeisel 2008, Shaw et al., 2004, 2006; Fischer et al., 2007;).

Gene PEMT: responsible for endogenous formation of choline

STUDY: effect of SNP (in ER (estrogen) binding site) within Promotor of the PEMT gene

Pregnant women with Loss of function allele In the gene PEMT need choline entirely from diet (eggs, liver, meat..

These usually not recommmended by physician, nutritionists

People and especially pregnana and postmenopausal women With the SNP rs12325817 polymorhism at higher risk

Page 8: Simon Horvat

•  How nutrients affect transcriptome, proteome, metabolome…

•  How gene variants respond (differentially) to nutrients

NUTRIGENOMICS NUTRIGENETICS

NUTRIGENOMICS

Mostly applies to: - an “average Homo sapiens” - of an average genotype - in an average environment

Mostly applies to: - Particular genotype

Very far from „personalised approach“

Page 9: Simon Horvat

HIGH PROTEIN vs CONTROL DIET

Rowlands D S et al. Physiol. Genomics 2011;43:1004-1020

©2011 by American Physiological Society

NUTRIGENOMICS – case study 1 TRANSCRIPTOME

Page 10: Simon Horvat

Effect of protein vs. control nutrition following intense endurance exercise on gene expression involved in protein modification and breakdown at 3 h postexercise.

Rowlands D S et al. Physiol. Genomics 2011;43:1004-1020

©2011 by American Physiological Society

Page 11: Simon Horvat

+ 0.15% cholesterol

+ 20% Picual olive oil (90 mg polyphenols/kg)

+ 20% Arbequina olive oil (25 mg polyphenols/kg)

+ 20% Palm oil

Polyphenols low

Polyphenols high

J. M. Arbones-Mainar….. B. Roos Journal of Proteome Research 2007, 6, 4041-4054

NUTRIGENOMICS – case study PROTEOME

Page 12: Simon Horvat

Proteome analysis by 2D gel electrophoresis

+ Olive Oil + Palm Oil

Overlay

-Identification of differentially expressed proteins -Quantification of differences

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80 proteins differentially expressed ( Olive oil vs. Palm oil )

Significant increases in the “Olive oil gropus) were observed in liver proteins for several : - antioxidant enzymes

-  enzymes of carbohydrate metabolism -  enzymes of the methionine cycle -  enzymes of glutathione synthesis

-Diminish oxidative stress -Slow down atherosclerosis

Page 14: Simon Horvat

NUTRIGENOMICS –METABOLOM

-Methods: mass spectrometer or nuclear magnetic resonance analysis (NMR). HUMAN METABOLOME DATABASE http://www.hmdb.ca/ -16.11. 2013, version 3.5 : ~ 41,511 entries of metabolites -Available databases suggest that there will be more molecules identified in future (with thousands more if bacterial metabolites are included).

METABOLOMICS: High through-put study of many small molecules formed by metabolism and relations between treatment and metabolome

Page 15: Simon Horvat

Biological samples for metabolomics

+ other tissues (liver….)

Blood Urine Saliva Spinal fluid

Griffin et al Metabolomics (2007) 3:179–188 On standardization of biological sample reporting

Page 16: Simon Horvat

METABOLOM– case study E. Chorell….. M. B. Svensson

Journal of Proteome Research 2009, 8, 2966-2977

OBJECTIVES: - Investigate if post-exercise ingestion of carbohydrates with proteins generates a different systemic metabolic response compared to carbohydrates or water.

4 tests of 90 min ergometer cycling Post exercise beverage/test Ingestion of different Beverages post exercise

Pre and post exercise Blood metabolom

GC-TOF Mass Spectroscopy

Page 17: Simon Horvat

Identified metabolites

……

Page 18: Simon Horvat

(A) Cross validated scores from a calculated OPLS-DA model describing the separation of subjects with high and low fitness level in the early recovery phase when ingesting water, that is, samples taken 15, 30, 60, and 90 min after performed exercise. Subjects with high fitness level (HighFit) are plotted as black circles while subjects with low fitness level (LowFit) are plotted as white dots. Corresponding LowFit subjects ingesting low carbohydrate−protein beverage (LCHO-P) following exercise were predicted into existing model and plotted here as gray dots. The corresponding LowFit subjects’ are connected with arrows. (Inset) Insulin concentration of LowFit subject with a deviating metabolic pattern when ingesting LCHO-P.

Published in: Elin Chorell; Thomas Moritz; Stefan Branth; Henrik Antti; Michael B. Svensson; J. Proteome Res. 2009, 8, 2966-2977. DOI: 10.1021/pr900081q Copyright © 2009 American Chemical Society

Nutritional modulation by Low carbohydrate-protein beverage ingestion was shown to improve the metabolic status of less fit subjects in the recovery phase.

Low fit subjects’ metabolome profile moved in the direction of the HighFit subjects, if they ingested macronutrients (low carbohydrates plus proteins) after exercise

High Fit - Water

Low Fit - Water

Low Fit + low carb./ PROTEIN

Two Low fit subjects with abnormal response after low carboh-protein intake -they had also high insulin increase and high level of metabolite myo- inositol

?Early indication of impaired insulin function or insulin resistance (BUT caution N = 2!)

High fit versus Low fit subject fell into separate clusters

Page 19: Simon Horvat

Relative mean concentration of resolved 3-methylhistidine (3-MeHis) (A) and pseudouridine (PSU) (B), from the GC−TOF MS data, after normalization by means of subtracting the detected concentration immediately after peformed exercise (0min) from the corresponing recovery time points, that is, 15, 30, 60, and 90 min in recovery. 3-MeHis decreases when ingesting a low carbohydrate−protein beverage whereas PSU increases, compared to the sole ingestion of carbohydrate or water.

Published in: Elin Chorell; Thomas Moritz; Stefan Branth; Henrik Antti; Michael B. Svensson; J. Proteome Res. 2009, 8, 2966-2977. DOI: 10.1021/pr900081q Copyright © 2009 American Chemical Society

Pseudouridine was suggested as a novel marker for pro-anabolic effect following Low carbohydrate-protein beverage ingestion, which was supported by the

detected decrease of the catabolic marker 3-methylhistidine.

decrease in 3-methylhistidine marker for protein (myofibrillar) breakdown

Pseudouridine, modified nucleoside - potential marker for increased protein synthesis, pseudouridine (PSU)

Page 20: Simon Horvat

De Filippo C et al. PNAS 2010;107:14691-14696 ©2010 by National Academy of Sciences

Life in a rural village of Burkina Faso.

DIET – GUT MICROBIOTA case study

African versus European children

Millet and Sorghum (high fiber staple diet)

Page 21: Simon Horvat

De Filippo C et al. PNAS 2010;107:14691-14696

©2010 by National Academy of Sciences

DIET – GUT MICROBIOTA case study

African versus European children

Rural African children

European children (mainly city of Florence)

Prevotella; Xylanibacter Cellulose, xylan hydrolisis Maximize E intake from fiber

Absent in EU kids

Page 22: Simon Horvat

short-chain fatty acids (SCFA)-producing bacteria could help to prevent establishment of some potentially pathogenic intestinal bacteria.

De Filippo C et al. PNAS 2010;107:14691-14696

©2010 by National Academy of Sciences

Quantification of SCFA in fecal samples Quantification of Enterobacteria potentially Causing diarrhea and gastrointestinal diseases

African children

EU children

African children

EU children

EU EU

EU EU

EU

EU EU

EU

Page 23: Simon Horvat

HORIZONTAL DNA

TRANSFER!!!!

HOW DID porphyranases from

marine bacteria ENDED up in the

Japanese gut bacterium B. plebeius

Bacteroides plebeius

Porphyra (red algae)

Page 24: Simon Horvat

Challenges - EPIGENETICS

Metilacija DNA (Citozinov)

Post-translacijske Modifikacije

Histonov (predvsem H3, H4)

Epigenetske spremebe DNA, proteinov – spremembe v izražanju

Encimi, ki dodajajo ali odstranjujejo

Epigenetske „značke“

Page 25: Simon Horvat

Challenges - EPIGENETICS Epigenetske spremembe zaradi OKOLJA tekom življenja

Gluckman_Beedle 2009 NATURE REV ENDO Epigenetic mechanism-metabolic-cardiovascular

? Mehanizem dedovanja epigenetskih spremembah (navadno par generacij) ? ncRNA, donor spermij?)

Page 26: Simon Horvat

Painter_ Roseboom 2008 Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life.". BJOG : an international journal of obstetrics and gynaecology 115 (10): 1243–9

Case - Dutch famine 1944-45 (500-1000 Kcal /day/person)

Challenges - EPIGENETICS

Page 27: Simon Horvat

http://www.precisionnutrition.com/epigenetics-feast-famine-and-fatness

Children of the women who were pregnant during the famine were smaller, as expected. However, surprisingly, when these women grew up and had children those grandchildren had increased neonatal adiposity and poor health in later. Six decades after being conceived during the Dutch hunger winter CHILDREN had less methylation on their IGF2 gene compared to their unexposed same-sex brother or sister. These data suggested that the famine experienced by the mothers in utero caused some kind of epigenetic changes that were passed down to the next generation.

Challenges - EPIGENETICS Case - Dutch famine 1944-45 (500-1000 Kcal /day/person)

Painter_ Roseboom 2008 Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life.". BJOG : an international journal of obstetrics and gynaecology 115 (10): 1243–9

Page 28: Simon Horvat

Challenges – better define DIET components

NAŠA TEKOČA ŠTUDIJA : testiranje

hipoteze

„pri inzulinski rezistenci povzročeni Z MAŠČOBNIMI

KISLINAMI deluje TLR4 »NIŽJE V KASKADI« od

ROSov.“

Pal s sod. NATURE MEDICINE 2012

Page 29: Simon Horvat

TEST DODATKA ANTIOKSIDANTOV? VPRAŠLJIVA PRIPOROČILA????

PROBLEM (PRAVILNO)sestaviti DIETO???? V komercialnih VIŠEK ANTIOKSIDANTOV, MINERALOV!!!!

CUSTOM  DIET  -­‐  HORVAT   #  gm%   kcal%  

Protein   23,0   20,0  Carbohydrate   45,0   40,0  Fat   20,0   40,0  Total   100,0   99,0  

Ingredient   gm   kcal  Casein   200,0   800,0  L-­‐CysOne   3,0   12,0  pure  starch   212,0   848,0  Maltodextrin   71,0   284,0  Sucrose   113,0   452,0  Cellulose   50,0   0,0  Choline  Bitartrate   2,0   0,0  Cholesterol   11,3   0,0  Custom  mineral  mix  Custom  Vitamin  mix  

Page 30: Simon Horvat

NUTRIGENOMICS –

VARIOME project

Ref. Kaput et al GENES AND NUTRITION Connecting the Human Variome Project to nutrigenomics (2010) Vol5 Pages: 275-283

Page 31: Simon Horvat

FINAL GOAL OF NUTRIGENETICS / NUTRIGENOMICS

Common changes in all “omics” platforms

Adapted from Mutch et al, FASEB 2005

UNRAVEL roles of nutrients in the bio- system IDENTIFY differential response of genotypes Fo

od c

ompo

nent

s, ad

ditiv

es, l

ifest

yle,

con

tam

inan

ts…

. DNA (SNPs)

RNA (Transcriptome)

PROTEIN (Proteome)

METABOLITES (Metabolom)

Bio-computations (Network Model)

Page 32: Simon Horvat

SKLEPI – NUTRIGENETIKA-NUTRIGENOMIKA

vplivi na prehranske potrebe •  (nutri“GENI“ velik vpliv, nepoznavanje! •  Trenutno TRANSLACIJA v PRIPOROČILA glede

na GENOTIP samo za REDKE gene –  (¸mutacije v PKU, galaktozemija, APOE, APOB…),kjer je

vpliv genotipa glavna determinanta prehranskega in zdravstvenega stanja

•  BODOČNOST - ? „Nutri podskupine“? •  NA KRATKI ROK: izobraževanje, podporne politike

za zdrav življenjski slog

Page 33: Simon Horvat

DANAŠNJE DEBELOSTNO OKOLJE

21 C 0

Page 34: Simon Horvat

PRITISK SOVRSTNIKOV, REKLAM (JE EVOLUCIJSKO „STARA“ LASTNOST)

LAHKO „POVOZI“ VSA SVETOVANJA STARŠEV

NUTRIGENETSKIH TESTOV ČE NI PODPORNIH POLITIK V DRUŽBI ZA VZGOJO

ZDRAVEGA ŽIVLJENJSKEGA SLOGA

Opice - Pritisk sovrstnikov.MOV

Page 35: Simon Horvat

DEBELOST = geni + okolje

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Page 37: Simon Horvat
Page 38: Simon Horvat

OBESITY

DEPTOR is inhibitor of mTor signaling pathway now linked also to OBESITY

Page 39: Simon Horvat

http://lollitop.magicgate.eu/

DEDIŠČINA VARČNIH GENOV Neel 1962: naravni izbor - “varčni” genotip!

10 MILJONOV LET ZADNJIH 100 LET

Page 40: Simon Horvat

DEDIŠČINA VARČNIH GENOV

10 MILIJONOV LET = 24 ur

SPREMEMBA DEBELOSTNO OKOLJE = zadnjih 8,6 sekund

Page 41: Simon Horvat

Pijača (0,33L):35 g slad. = 150 Kcal Medaljoni (200g) 500 Kcal Pomfrit (169g) 519 Kcal SKUPAJ: 1169 Kcal

Genotip X Okolje – zadnjih 50 let

Page 42: Simon Horvat

G*O - AGRESIVNE ZAVAJUJOČE REKLAME

Page 43: Simon Horvat

BIOTEHNOLOŠKO PRIDELANO MESO???

Page 44: Simon Horvat

BIOTEHNOLOŠKO PRIDELANO MESO???

http://culturedbeef.net/

? Cena/burger

$ 330 000

Page 45: Simon Horvat

The promise of personalised medicine 20 YEARS AGO

•  “In the not-so-distant future, we can expect to walk into a physician’s office for an annual physical examination and walk out with a blueprint of our genetic inheritance – and with the knowledge of the most likely cause of our own death”

•  Henig RM: High tech fortune telling. The New York Times, NY, USA page 6, 24. December 1989

Page 46: Simon Horvat

275 URLs

HEALTH TESTS -disease genes -pharmacogenetic (e.g. P450 2D6) -~30 to 1200 clinical conditions

NUTRITIONAL -nutrigenetic -nutrigenomic -Diet and metabolic profiling

SOCIAL-GENETIC - ancestry -prenatal sex deter. -semen detection -Infidelity tests

STATUS: WHAT IS OFFERED adapted from Sterling, Genetic in Medicine 2008 and other

Page 47: Simon Horvat

STATUS – WHERE is offered

Reference: adapted from Sterling, Genetics in Medicine 2008 and others

TYPES OF ORGANISATIONS

COMPANIES -Biotech comp. -Laboratories -Testing facil.

HEALTH CARE PROVIDERS WITH DOCTOR -Biotech comp. -Laboratories -Testing facilities

WELLNES CARE PROVIDERS -Biotech comp. -Laboratories -Testing facilities

e-VENDOR -Pharmacies -Drugstores

OTHER -Consumer org. -Non-profit org.

26 % 17 % 33 % 11 % 13 %

Page 48: Simon Horvat

Web based Personalised medicine

2

SEND SALIVA BY POST

200

$ 200

Page 49: Simon Horvat

NUTRIGENETICS – genotype PPARG – MUFA (Mediterranean diet)

Gen: PPARG

Page 50: Simon Horvat

Gen: APOA2

NUTRIGENETICS – genotype APOA2 – dieta bogata z nasičenimi maščobami

Page 51: Simon Horvat

Gen: APOA5

NUTRIGENETICS – genotype APOA5 – dieta bogata z maščobami (30% kalorij iz maščob ali več)

Page 52: Simon Horvat

NUTRIGENETICS – genotype TAS2R38– APETIT

Gen: TAS2R38

Page 53: Simon Horvat

NUTRIGENETICS – SNP v 8q14– rak na prostati

Priporočila za osebo , ki je nosilec mutantnega alela

Page 54: Simon Horvat

Odds calculations

Marker effects

Page 55: Simon Horvat

Odds ratios - Razmerje obetov Razmerje obetov (OR) pomeni, da je verjetnost, da se bo nek dogodek zgodil v eni skupini 1, 2, 3-krat večji kot v drugi skupini. Npr., če je razmerje obetov pri neki bolezni za Alel A proti alelu T enako 1,42, pomeni, da se bo v tej populaciji pojavljal 1,42- krat bolj pogosto pri obolelih kot pri zdravih osebkih

Vmesna razlaga

Page 56: Simon Horvat

Odds ratios - Razmerje obetov Razmerje obetov (OR) pomeni, da je verjetnost, da se bo nek dogodek zgodil v eni skupini 1, 2, 3-krat večji kot v drugi skupini. Npr., če je razmerje obetov pri neki bolezni za Alel A proti alelu T enako 1,42, pomeni, da se bo v tej populaciji pojavljal 1,42- krat bolj pogosto pri obolelih kot pri zdravih osebkih

Vmesna razlaga

Page 57: Simon Horvat

Vmesna razlaga

Example Suppose that in a sample of 100 men, 90 have drunk wine in the previous week, while in a sample of 100 women only 20 have drunk wine in the same period. The odds of a man drinking wine are 90 to 10, or 9:1, while the odds of a woman drinking wine are only 20 to 80, or 1:4 = 0.25:1. The odds ratio is thus 9/0.25, or 36, showing that men are much more likely to drink wine than women. Using the above formula for the calculation yields the same result:

The above example also shows how odds ratios are sometimes sensitive in stating relative positions: in this sample men are 90/20 = 4.5 times more likely to have drunk wine than women, but have 36 times the odds. The logarithm of the odds ratio, the difference of the logits of the probabilities, tempers this effect, and also makes the measure symmetric with respect to the ordering of groups. For example, using natural logarithms, an odds ratio of 36/1 maps to 3.584, and an odds ratio of 1/36 maps to −3.584.

Log(2) = 3,58

Male

Fem.

Male Fem. 0.2 / 0.8

0.9 / 0.1 1 / 36 Log(2) = -3,58

Odds ratios - Razmerje obetov

Page 58: Simon Horvat

Allelic odds ratios (razmerje obetov)

SNP v genu Alel, ki veča ITM

Drug alel OR – rizik za prekomerno

težo

OR – rizik za debelost

FTO A T 1,14 1,25

TMEM18 C T 1,13 1,19

MC4R C T 1,07 1,15

GNPDA2 ….

G A 1,08 1,12

Page 59: Simon Horvat

PRIMER IZRAČUN RAZMERJA OBETOV

AA AT TT

Normalna teža

20 33 6

Debelost

110 167 80

A T

Normalna teža

A 40+33=73

b 33+12=45

Debelost C 220+167=387

D 160+167=327

OR= 73:45 / 387:327 = 1,38

Frekvence GENOTIPOV

Frekvence ALELOV

Page 60: Simon Horvat

Current status – BAD EXAMPLE –Sciona Personalised nutrition

Page 61: Simon Horvat

BAD EXAMPLE –Sciona Personalised nutrition

Page 62: Simon Horvat

BAD EXAMPLE –Sciona Personalised nutrition and Lifestyle

PROBLEMATIC: -TO FEW GENES ANALYSED (28) -RESULTS HEAVILY BASED ON QUESTIONNAIRE -INTERPRETATION AND RECOMMENDATIONS OVER AMBITIOUS AND IN PART QUESTIONABLE

Page 63: Simon Horvat

NUTRIGENETICS – examples from companies selling nutrigenetic tests

GENOVA DIAGNOSTICS http://www.genovadiagnostics.com

……

Page 64: Simon Horvat

NUTRIGENETICS – examples from companies selling nutrigenetic tests

INTERLEUKIN GENETICS http://www.ilgenetics.com

Genetic variations (MTHFR) have been shown to prevent appropriate utilization of vitamins B-6, B-12 and folate in one-carbon metabolism

MTHFR 677 C>T variant genotypes disrupts Homocystein metabolism, methylation of proteins, DNA and phospholipids in cells and is associated with certain disease states.

TREATMENT OPTION: Increasing plasma levels of vitamins B-6, B-12 and folate will benefit persons carrying MTHFR 677 C>T genetic variations.

NTD = neural tube defect

CHD = coronary

heart disease

Page 65: Simon Horvat

NUTRIGENETICS- GOOD EXAMPLE –Choline SNPs

Big Study - Pregnant women in California -too low choline in 25% women (high correlation to PEMT SNP

--à birth defects (Sha et al 2010; Zeisel 2008, Shaw et al., 2004, 2006; Fischer et al., 2007;).

Gene PEMT: responsible for endogenous formation of choline

STUDY: effect of SNP (in ER (estrogen) binding site) within Promotor of the PEMT gene

Pregnant women with Loss of function allele In the gene PEMT need choline entirely from diet (eggs, liver, meat..

These usually not recommmended by physician, nutritionists

People and especially pregnana and postmenopausal women With the SNP rs12325817 polymorhism at higher risk

Page 66: Simon Horvat

NUTRIGENETICS- NUTRIENT PROFILING – NUTRIENT COUNCELLING– case study

OBJECTIVES OF THE STUDY 1.) compare

- a.)the personalized dietary recommendations suggested by a commercial nutri genomic and nutrigenetic test kit, the G-profile with - b) the recommendations based on 2 different, widely used Nutritional Profiling schemes usually taken as references

2.) to calculate genetic test-NP agreement regarding the suitability of 50 commonly eaten foods.

Gregori D, Foltran F, Verduci E, Ballali S, Franchin L, Ghidina M, Halpern GM, Giovannini M: A Genetic Perspective on Nutritional Profiles.. J Nutrigenet Nutrigenomics 2011; 4:25-35

Page 67: Simon Horvat

NUTRIGENETICS- NUTRIENT PROFILING – NUTRIENT COUNCELLING– case study

DATA COLLECTION 12 normal-weight and 12 overweight children, matched by age and gender, were recruited in the Trieste district Nutrigenetic testing was offered to them using the G-Diet® Nutrigenomic Kit. The parents of all study participants signed a consent form

Gregori D, Foltran F, Verduci E, Ballali S, Franchin L, Ghidina M, Halpern GM, Giovannini M: A Genetic Perspective on Nutritional Profiles.. J Nutrigenet Nutrigenomics 2011; 4:25-35

Page 68: Simon Horvat

NUTRIGENETIC- NUTRIENT PROFILING – NUTRIENT COUNCELLING– case study

Gregori D, Foltran F, Verduci E, Ballali S, Franchin L, Ghidina M, Halpern GM, Giovannini M: A Genetic Perspective on Nutritional Profiles.. J Nutrigenet Nutrigenomics 2011; 4:25-35

Individual Nutrigenetic test results

Favourable alleles Less Favourable alleles Average alleles

M = male, F = female; S = sensitive allele NS non-sensistive; NT non-taster; Mt medium taster; ST supertaster

Child 1 Child 2 Child 3 Child 4 Child 5 Child 6 Child 7 Child 8 Child 9

Child 10 Child 11 Child 12

Page 69: Simon Horvat

NUTRIGENETICS- NUTRIENT PROFILING – NUTRIENT COUNCELLING– case study

Gregori D, Foltran F, Verduci E, Ballali S, Franchin L, Ghidina M, Halpern GM, Giovannini M: A Genetic Perspective on Nutritional Profiles.. J Nutrigenet Nutrigenomics 2011; 4:25-35

Nutritional Profiling schemes

Nutrigenetic test recommmendatinos

Food recommended

Food not recommended

Page 70: Simon Horvat

NUTRIGENETICS- NUTRIENT PROFILING – NUTRIENT COUNCELLING– case study

Gregori D, Foltran F, Verduci E, Ballali S, Franchin L, Ghidina M, Halpern GM, Giovannini M: A Genetic Perspective on Nutritional Profiles.. J Nutrigenet Nutrigenomics 2011; 4:25-35

1. ) (Dis)Agreement between the 2 NUTRITIONAL PROFILING SCHEMES -VERY POOR CORRELATION

-average coefficient 0,66, especially low for cereals, milk products and drinks (below 0.5) “CLASSICAL NUTRITIONAL PROFILING” questionable as they assume average dietary requirements resulting in inappropriate diet recommendations

CONCLUSIONS

2. ) Agreement between the NUTRIGENETIC TEST predicitions and 2 NUTRITIONAL PROFILING SCHEMES variable (from 0.3 to 0.8) -NUTRIGENOMIC TESTING PROMISING IN THAT IT CAN COPE WITH GENETIC HETEROGENEITY BUT STILL A LONG WAY TO BECOME A GOLD STANDARD

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PODJETJA PRI NAS NUTRIGENETIKA-NUTRIGENOMIKA

http://www.nutrigenomika.info/kdo_smo.htm

Kako poteka določanje vašega nutrigenomičnega profila® Najprej boste predložili osebne podatke in izpolnili nekaj vprašalnikov v zvezi z vašim zdravstvenim stanjem ter dosedanjimi navadami glede prehrane in načina življenja. Bistven podatek za določanje vašega nutrigenomičnega profila® je vaša krvna skupina po sistemu ABO in Rh faktor, zato morate predložiti potrdilo o vaši krvni skupini ABO in Rh faktorju, ki ga izda zdravnik ali ustrezna zdravstvena ustanova.

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PODJETJA PRI NAS NUTRIGENETIKA-NUTRIGENOMIKA

http://www.nutrigenomika.info/kdo_smo.htm

Kako poteka določanje vašega nutrigenomičnega profila® Najprej boste predložili osebne podatke in izpolnili nekaj vprašalnikov v zvezi z vašim zdravstvenim stanjem ter dosedanjimi navadami glede prehrane in načina življenja. Bistven podatek za določanje vašega nutrigenomičnega profila® je vaša krvna skupina po sistemu ABO in Rh faktor, zato morate predložiti potrdilo o vaši krvni skupini ABO in Rh faktorju, ki ga izda zdravnik ali ustrezna zdravstvena ustanova.

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PODJETJA PRI NAS NUTRIGENETIKA-NUTRIGENOMIKA

http://lifegenetics.eu/pogosta-vprasanja/nutrigenomika/

POMEMBNO OPOZORILO! NUTRIGENOMIKA, NUTRIGENOMIČNI PROFIL in drugi izpeljani izrazi se v Sloveniji pogosto zlorabljajo. Pri nakupu bodite pozorni, da izvajalec nutrigenomske analize dejansko opravlja analizo genov oz. DNK test in ne le analizo krvne skupine. Velik indikator prevare je že dejstvo, da izvajalec za opravljanje storitve potrebuje odvzem krvi z namenom določitve krvne skupine. Za GENSKO ANALIZO ODVZEM KRVI NI POTREBEN in je prava redkost.

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STRENGHTS – HP vs. DTC

•  Doctor and other professionals involved (dietitian, geneticists)

•  Likely more regulatory control (?)

•  Better data safety (?) •  Follow up procedures not left to

consumer decision

•  Easy access at will •  Greater consumer involvement – •  Greater potential for education –

better interaction with physicians

•  Data there for future review, re-interpretation without the need to ask physician

“Official health providers “Direct-to-consumer companies

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Cahill LE, Fontaine-Bisson B, El-Sohemy A: Functional genetic variants of glutathione S-transferase protect against serum ascorbic acid deficiency. Am J Clin Nutr 2009; 90: 1411–1417. Xie L, Innis SM: Genetic variants of the FADS1 FADS2 gene cluster are associated with altered (n-6) and (n-3) essential fatty acids in plasma and erythrocyte phospholipids in women during pregnancy and in breast milk during lactation. J Nutr 2008; 138: 2222–2228. Yuan J-M, Koh W-P, Sun C-L, Lee H-P, Yu MC: Green tea intake, ACE gene polymorphism and breast cancer risk among Chinese women in Singapore. Carcinogenesis 2005; 26: 1389–1394. Petermann I, Triggs CM, Huebner C, et al: Mushroom intolerance: a novel diet-gene interaction in Crohn’s disease. Br J Nutr 2009; 102: 506–508.

NUTRIGENETICS –

4 additional „good“ case studies

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NUTRIGENOMICS – case study 2 TRANSCRIPTOME

HUMANS - OLIVE OIL (POLYPHENOLS) – MEDITERRANEAN DIET - TRANSCRIPTOME

Konstantinidou, Valentini; Covas, Maria-Isabel; Munoz-Aguayo, Daniel; et al. In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: a randomized controlled trial FASEB JOURNAL Volume: 24 Issue: 7 Pages: 2546-2557 JUL 2010

TMD – traditional Mediterranean diet (instructed, e.g.,. the use of olive oil for cooking to dress vegetables, pasta, rice; increased consumption of fruit, vegetables, and fish; homemade sauce with tomato, garlic, onion, aromatic herbs, and olive oil, white > red meat, moderate consumption of red wine. WOO = VOO but less polyphenols (55 and 328 mg/kg, respectively)

DESIGN-OBJECTIVE:

Group 1, TMD with virgin olive oil (TMD-VOO) group 2, TMD with washed virgin olive oil (TMD-WOO) group 3, control group with their habitual

VOO = Virgin Olive Oil

WOO = Washed Olive Oil

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HUMANS - OLIVE OIL (POLYPHENOLS) – MEDITERRANEAN DIET - TRANSCRIPTOME

VOO WOO

VIRGIN OLIVE OIL – significant effect of POLYPHENOLS more so than MUFA (in TMD) Beneficial effects on expression of -inflammatory genes; oxidative stress, metabolic stress transcriptome

Peripheral Blood Monocyte expression

VOO WOO CONTROL CONTROL

PRO-ATHEROGENIC GENES DOWNREGUlATED