Beslenme ve Nutrigenetik: Dnyadaki

Gncel Uygulamalar

Yrd. Do. Dr. Nesrin Erelen

Baheehir niversitesi, Tp Fakltesi, Tbbi Genetik ABD
 Nutrigenetik,
metabolizmann kullanlan
diyete ve beslenme
alkanlklarna kar verdii
cevabn zerine genetik
varyasyonlarn etkisini ve
besin maddeleri ile
biyoaktif yiyecek
ieriklerinin genetik
ekspresyona etkisini
inceleyen bilim daldr.
 Nutrigenetii nemli bir bilim dal yapan temel faktr
vardr;
Bireylerin, besin maddelerinin biyo-yararll ve metabolizmay
etkileyen kaltnm genomu arasnda byk bir eitlilik vardr,
insanlarn kltrel, ekonomik, corafi ve tat algs farkllklarna
bal byk tercih farklar ve yiyecek/besin maddesi
bulunurluu farklar vardr,
beslenme bozukluu (yetersizlii veya fazlal) gen
ekspresyonunu ve genom kararlln etkileyebilir ve gen
sekansnda veya kromozomal seviyede mutasyonlara sebep
olarak anormal gen dozajlarna ve gen ekspresyonuna sebep
olarak hayatn eitli dnemlerinde farkl fenotiplerin
olumasna nclk edebilir.
Nutrigenetik
Genler, hcre ekirdeinin i faktrlerden
(hormonlar) ve d faktrlerden (besin maddeleri)
aldklar metabolik sinyallere gre alp
kapanabilirler.

Evrimsel geliimde organizmann sindirdii besin

maddeleri, ktlk ve bolluk zamanlarnda, sentez ve
depolama yollarn ap kapatabilecek primitif
sinyaller olarak ilev gstermilerdir.
 Bylelikle genomlar
beslenme
alkanlklarn da ieren
birok farkl evresel
uyarana gre
evrilmitir. Bu yzden
genetik bilginin
ekspresyonu, besin
maddelerine,
mikrobesinlere ve
yemeklerde bulunan
fitokimyasallara byk
lde bal olarak
dzenlenebilir
 Besin gen etkileimi yolla oluur:
1) Direk etkileim: besin maddeleri bazen bir reseptr ile etkileerek
DNAya balanabilen bir transkripsiyon faktr gibi davranabilir ve gen
ekspresyonunu indkleyebilir. rnein, A vitamini ya da A vitaminin
retinoid trevleri retinoid asit reseptr proteinleri ile etkileerek
genlerin promotr blgelerine balanarak transkripsiyonu aktive
edebilir veya basklayabilir.
2) Epigenetik etkileim: besin maddeleri DNAnn yapsn
deitirebilir ve gen ekspresyonu kronik olarak deiir.
Epigenetik mekanizmann srekli etkisi DNA metilasyonu,
asetilasyonu veya histon biyotinasyonu araclyla yaplr.
Sonuta ortaya kan epigenetik modifikasyon, kiinin hayat
boyunca hatta gelecek kuaklarnda var olacak ekilde gen
ekspresyonunu deitirebilir.
3) Genetik varyasyon: yaygn genetik varyasyonlar
(SNPler) genlerin fonksiyonlarn veya ekspresyonlarn
deitirebilir. Bu mekanizma, deimi mekanizmalar
ile ve besinsel gerekliliklerin deiimi ile sonulanabilir.
Inslin Metabolizmas
KLNK NUTRGENETK
Nutrigenetiin uygulamalar, genetik yatknln,
beslenme ile ilgili mdahaleler ile hafifletilebilen
hastalklara kullanmn kapsar.

Gda endstrisini iin nutrigenetiin potansiyeli

bilimsel hedefler iin formlize edilmi gzel tatl
rnler salanmasdr.
 Hali hazrda eitli besin maddeleri ile hastalklar
iyiletirmek veya hastalklardan korunmak zere
zenginletirilmi fonksiyonel yiyecekler
bulunmaktadr. Son zamanlarda incelenen bir alan
da, rnlerin omega-3 ya asitleri ile
zenginletirilmesidir
 Belirli bir hastala maruz kalm bireylerin, ailelerin
ve alt gruplarn tedavisi iin veya koruyucu ajanlar
olarak yiyecek ve iecekler gelitirilebilir. rnek
olarak, pediyatride epilepsi hastas bireylerin
tedavisinde ketojenik besinler kullanlmaktadr.
 Artrit, astm, lseratif
kolit, lupus vb. kronik
inflamatuvar
hastalarda olduu gibi
koroner arter ve
hipertansiyon
hastalarnda da arka
plan diyeti olarak
temel ya asitlerinin
dengelendii bir diyet
kullanlmas ok
nemlidir.
 lyak (celiac)
hastalarnda,
fenilketonri
hastalarnda ve dier tek
gen hastalklarnda hali
hazrda spesifik yiyecek
ve diyetler
kullanlmaktadr.
 Medicinal
Genetics
Department

Personalized Health Management

Genetic counseling/examination
Medicinal Biochemistry of blood
Genetics
Department DNA analysis
Personel report

Personalized health monitoring and treatment strategy

Medicinal Nutrigenetics
Genetics Pharmacogenetics
Department
Medical treatment
Surgery treatment

Medicinal
Genetics
Department
 Medicinal
Genetics
Genetic Counseling
Department

Medicinal
Genetics
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Family pedigree
Medicinal
Genetics
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Medicinal
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 Medicinal
Genetics
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Genetic Testing

Medicinal
Genetics
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Medicinal
Genetics
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And sent to the

Blood laboratory for
sample is genetic testing
Medicinal taken
Genetics
Department
 Medicinal
Genetics
Department

APPENDIX: HOW TO READ THE GENOTYPE REPORT (EXAMPLE)

Gene Polymorphism
Medicinal Gene Presence Presence
Symbol Allele 1 > Allele 2
of Allele 1 of Allele 2
Genetics
Department
GENE NAME X GName X b>B X

Gene Genotype
Presence Presence
Genotype description
Symbol Allele 1 > Allele 2
of Allele 1 of Allele 2

GName X
HOMOZYGOUS ALLELE 1 bb / - X
Medicinal
Genetics GName X
HOMOZYGOUS ALLELE 2 - / BB X
Department

HETEROZYGOUS GName X b / B X X

Medicinal
Genetics
Department
 GENOTYPE REPORT
Medicinal 1. ARTERIOSCLEROSIS / LIPID METABOLISM
Genetics
Department Gene Polymorphism Presence Presence
Gene
Symbol Allele 1 > Allele 2 of Allele 1 of Allele 2

Apolipoprotein A1 APOA1 G>A Pos. -75 Promoter X X

Apolipoprotein E APOE Cys>Arg Codon 112 X

Apolipoprotein E APOE Arg>Cys Codon 158 X X

Medicinal
Cholesterol ester transfer protein CETP Arg>Gln Codon 451 X
Genetics
Department
Sterol element binding transcription factor SREBF2 Gly>Ala Codon 595 X

Endothelial NO-Synthase NOS3 T>C Pos. -786 Promoter X

Endothelial NO-Synthase NOS3 Glu>Asp Codon 298 X

Medicinal
Genetics
Department Endothelial NO-Synthase NOS3 Ins>Del Intron 4 (VNTR) X

Gap junction protein alpha 4 (Connexin 37) GJA4 Pro>Ser Codon 319 X X

Matrix metalloproteinase 3 (Stromelysin 1) MMP3 5A>6A Pos. -1171 X

Medicinal Paraoxonase 1 PON1 Gln>Arg Codon 192 X

Genetics
Department
 7. Metabolism and Obesity
As for the blood pressure you display a high risk of left ventricular hypertrophy
Medicinal due to the homocygoty of the GNB3. It is a signal protein, which works too
Genetics hard.
Department
In addition I include a study, which gives sufficient risk explaining. Please keep
ypour blood pressure low!(<120/80)

A common C825T polymorphism in the gene GNB3, which encodes the beta 3
subunit of heterotrimeric G proteins, was identified in cell lines from patients
Medicinal
Genetics with hypertension. The 825T allele is associated with increased intracellular
Department signal transduction. Many population-based and case-control studies in
different ethnicities have investigated an association between this
polymorphism and hypertension, obesity, and atherosclerosis. A critical
assessment of published studies suggests that 825T allele carriers have
an increased risk for hypertension combined with features of the
metabolic syndrome, such as dyslipidemia, hypercholesterolemia, insulin
Medicinal
Genetics resistance, and obesity. It is anticipated that this polymorphism will be
Department used in clinical practice to better characterize hypertension and for
individualized treatment regimens.

For diet: low glyceamic diet(see below)

The ADRB2 variant increases the risk of obesity and metabolic syndrome. This
Medicinal
is to say as well regarding the PAI-1 . The MTHFR produces slightly increased
Genetics Homocystein levels. They can be cured by a mixture of Vitamin B12, B6, Folic
Department acid and Same.
 Medicinal
CORONARY ARTERY DISEASE (CAD)
Genetics
Department

The association of GENETICS and ENVIRONMENT

Medicinal Healthy Unhealthy

Genetics
Department
Good genes Low CAD Low CAD

Bad Genes Low CAD High CAD

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 Medicinal
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Polymorphisms

Medicinal
Genetics
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Environmental factors

Medicinal
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Expression of genetic polymorphisms

Atherosclerosis and CAD
Medicinal
Genetics
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 Medicinal
Ageing Process and Symptoms
Genetics
Department

The ageing process occurs over

all the body and for everyone,
but the pace may be different
depending on the type of organ
Medicinal or individual. Certain cells in our
Genetics tissues simply stop working
Department after a while. When enough
tissue is rendered dysfunctional,
we come face to face with the
debilitation of ageing. However,
these cell deaths do not happen
all at the same time. Some
tissues remain viable for many
Medicinal
decades, some wear out rather
Genetics
quickly. And ageing does not
Department
occur in the same way in every
human being. It turns out that
people's lifestyles also has
additional influence on ageing.

Medicinal
Genetics
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What is Personalized Medicine?

The Human Genome was

sequenced by the year 2000 at a
cost of about
$2.7 billion

Personalized Medicine is
the
Human Genome Project
Dividend
Personalized Medicine:

What is it?
 How Has Genomics Enabled
Personalized Medicine?
Medicinal
Genetics
Department Genomics has led us to a better understanding of the
molecular signals of disease

Medicinal
Genetics Genes
Department
Clinical data

Medicinal Proteins Molecular screens combined

Genetics
Department with clinical data will point to more
precise treatment options for each
individual patient

Medicinal
Metabolites
Genetics
Department
 Modern Medicine
Medicinal
Genetics
Department
DNA MEDICINE
1- Individual patient
is taken care
Medicinal
Genetics
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2- Genetic
technology

Medicinal
Genetics
3- Informative
Department
consultation:
Patients give the
decision
Medicinal
Genetics
Department
 The Future of Medicine

Newborn screening expands to

track hundreds or thousands of
genes, rather than dozens.
Information is used throughout
the individuals life to manage
their healthcare.
Medical information on a smartcard
contains our unique molecular profile.
Healthcare providers will consult the
profile before treatments/drugs are
prescribed.

Blood and other samples drawn

during routine medical visits are
submitted for molecular
screening for a large number of
cardiovascular, cancer,
neurological and other diseases
that may develop
U.S. Department of Energy Human Genome Program
http://www.ornl.gov/hgmis
U.S. Department of Energy Human Genome Program
http://www.ornl.gov/hgmis
SNPs and HUMAN POPULATION

Number of Possible genotypes Number of

SNPs (bi-allelic people
calculation) (8 billion people)

10 1.024 7.812.500
15 32.768 244.141
20 1.048.576 7.629
25 33.554.432 238

30 1.073.741.824 7

33 8.589.934.592 <1

All calculations are based on the assumption,

that these SNPS are not linked
 What is Personalized Medicine?
Medicinal
Genetics
Department
Current Practice Personalized Medicine

One size fits all

Medicinal
Genetics
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Medicinal
Genetics
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Trial and Error The right treatment for
the right person at the
right time
Medicinal
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 Major Drugs Ineffective for Many
Medicinal
Genetics
Department Hypertension Drugs 10-30%
ACE Inhibitors

Heart Failure Drugs 15-25%

Medicinal Beta Blockers
Genetics
Department

Anti Depressants 20-50%

Medicinal Cholesterol Drugs 30-70%

Genetics
Department Statins

Asthma Drugs 40-70%

Beta-2-agonists
Medicinal
Genetics
Department
 And Harmful to Some
Medicinal
Genetics Just in hospitals: about 6.7% of patients (2.2 million)
Department
experience serious adverse drug reactions

Medicinal
Genetics
Department
Serious adverse drug reactions in even smaller
percentages of treated populations have led to the
withdrawal of several drugs from the market
Fen-Phen
Medicinal
Baycol Lotronex
Genetics
Department
Are good drugs going to the wrong people?

Propulsid Vioxx
Tysabri
Medicinal
Genetics
Department
OSTEOPOROSIS
Col1A1 Type I collagen
Vitamin D Receptor VDR
BLOOD CLOTTING RISK
Prothrombin- F2
PAI 1- Plasminogen Activator
Inhibitor Type I
Factor V Leiden
Glycoprotein IIIA GPIIIA
MTHFR GENE
INFLAMMATION
Interleukin 6 - (IL-6)
Interleukin 10- (IL10)
DETOXIFICATION
Glutathione S-transferase pi- (GSTP1)
Glutathione S-transferase M1 -(GSTM1)
HYPERTENSION
Angiotensin Converting Enzyme- (ACE)
Angiotensinogen- (AGT)
-Adrenergic Receptor - (ADRA2B)
-Adrenergic Receptor- (ADRB1)
S
N
P
METABOLISM AND OBESITY
G Protein 3-subunit- (GNB3)
Neuropeptide Y (NPY)
-Adrenergic Receptor- (ADRB2)
-Adrenergic Receptor- (ADRB3)
Cholesterol Ester Transfer Protein-(CETP)
Sterol Regulatory Element Binding
Transcription Factor 2 (SREBF2 )
Endothelial NO-Synthase- (NOS3)
Gap Junction Protein alpha 4 (GJA4)
Matrix Metalloproteinase 3 (MMP3)
Paraoxonase 1- (PON1)
Preimplantation Genetic Diagnosis

Embryo Fetus
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 Medicinal
IMAGES of FISH ANALYSIS
Genetics
Department

PB Probe mixture :
Medicinal
Genetics
Department Chromosome 13 x3
Chromosome 16 x2
Chromosome 18 x2
Chromosome 21 x2
Chromosome 22 x2
Medicinal
Genetics
Department

Blastomere with Trisomy 13

Medicinal
Genetics
Department
PERSONALIZED
MEDICINE

REGENERATIVE
MEDICINE: STEM
CELL

PREVENTIVE
GENETIC
DIAGNOSIS