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Lecture 11 Gene and nutrition
Genetic
factor
Non-esterified
fatty acid
rise in blood
Hyperlipemia
Oxidation Ripo
protein
Lifestyle related
factor
Obesity
Insulin
resistance
Abnormal
glucose
tolerance
hyperinsulinemia
Hypertension
Salt collect.
Sympathetic
nerve tension
Right figure shows the structure of DNA
(deoxyribonucleic acid). All genetic codes
of the living thing are decided by how of
four kinds of bases such as A, G, C, and T
to queue up. Only in the array of only two
kinds of 0 and 1, the computer is the
same as can show all sentences and
figures
All genetic codes of one cell are called a
genome, and the same genome as each
one of 60 trillion that make the body
exists. Because the genome is a blueprint
of the whole body, the cloned sheep can
make it from sheep's one soma.
Nutrigenomics is a compound word of
Nutrition (nourishment) and Genomics
(genome analysis)
Double stranded of DNA is mutually copied
and is inherited
Guanine Cytosine
Hydrogen
bond
Direction of DNA strand
G-C：３
DNA of parents cell
A-T：２
Division
The corresponding
bases are united
DNA of
Child cell
Double-standard
DNA
Phosphoric
acid
Adenine
Nucleotide
It dissociates into
single stranded DNA
Pentose
Base
Guanine Cytosine
Base
Complementary
Pentose
Chain DNA
Phosphoric
against up
acid
Cytosine Guanine
Hydrogen bond
Thymin Adenine
Single-standard
DNA
Yasuo KAGAWA et at al. “Core, molecular
biology of human body” MARUZEN, 1997, p.2
Identical twin's identity frequency of the attack is higher than that of fraternal twins.
Monovular brother's one side is a possibility of the prevention of the high rate
because it doesn't get sick
Both brotherly appearance of
disease frequency of twin
Identical twin
（Men62 Women63）
ＢＭＩ
Blood sugar rise for
120 minutes
Systolic pressure
Diastolic blood pressure
Value of HDL cholesterol
0.68
0.52
0.55
0.47
0.61
Homosexual fraternal twins
（Men86 Women92）
0.28
0.26
0.17
0.07
0.26
Statistical,
significant difference
ｐ value
<0.001
<0.05
<0.001
<0.01
<0.001
Article ： P.Poulsen et al. Diabetologia 44:537-543 (2001)
An increase in disease by making of meal European-style
Comparison of 3 groups (40 or more) in Hisayama-machi
Age
adjustment
person
Hyperlipemia:Total cholesterol
Frequency
per 1961
per 1961
Kyushu University the second internal medicine department
Hisayama laboratory
Women
Men
(To Cerebral infarction
Abnormal
glucose
Tolerance
(To Cerebral infarction
Cardiac infarction)
(To diabetics)
Cardiac infarction)
Hyperlipemia
Hyperlipemia
Abnormal
glucose
Tolerance
(To diabetics)
Relation between strength to alcohol and gene
Base
Normal type
Amino acid
Of enzyme
Threonine
Glutamic
acid
Valin
Lysine
Threonine
From father
Strong
Deletion form
from mother
Normal type / Normal type
Middle Deletion form / Normal type
single
nucleotide
polymorphism
Weak Deletion form /Deletion form
Lysine
Distribution of aldehyde dehydrogenase multi type and
consumption of ethanol. It is small in a lot of Japanese Yayoi
Kinki, China, and Hokuriku that is
Hokkaido
gene
Tohoku
Hokuriku
Kanto
Chugoku
North
kyushu
EthanolYear/person)
Hokkaido
Tohoku
Kanto
Chubu
Hokuriku
Kinki
Chugoku
North
Kyushu
Shikoku
South kyushu
Okinawa
Kinki Chubu
frequency
Amount of Alcohol consumption
Shikoku
South
Kyushu
Each prefecture investigated for 5000 Japanese or more in total
Feature of gene polymorphism related to
nourishment in Japanese
1.The hunger tolerance: Light obesity is a diabetic and infarct: βARs
and UCPs.
2. The salt receptivity: It is high blood pressure by 10g or more on the
salt
the first: TT type of AGT.
3. Alcoholic receptivity: The weak person is a cancer of the esophagus
in alchol: Two types of ALDH2.
4.No lactose tolerance: Limit 500ml of for drinking milk: Adult lactase
loss
5.A passive, joint character: Guidance politely :: The SS type of
SerotoninT.
6.Folic acid and Epijeneticcs: Acknowledgment syndrome and cerebral
infarction: TT type of MTHFR
7.The amount of the pancreatic island secretion: It is diabetic
constitution half of Caucasian: Multi type of SOCS2.
8.Detoxication Nou uniqueness: Racial difference of food function
element effectiveness: CYP multi type
9.Haplotype of mitochondria: New mongoloid feature
DNA
Self
prolification
Reaction of
S period
(DNA Polymerase α)
DNA reproduction
RNA transcript
Protein translation
Disease and gene
information
Replication
Gene type
(Mutation)
Change of
nucleotide sequence
Chromosome)
Transcription
polymerase
Addition (Cap, Poly A)
Splicing
Abnormal regulation
Of expression
(Steroid hormone action, etc)
Processing abnormal
Of the translation product
(Thalassemia, etc )
Yasuo KAGAWA et at al. “Core, molecular
biology of human body” MARUZEN, 1997, p.16
Peptide
bond
Messenger RNA
Translation
Synthesis protein (Start, Extension, Conclusion)
Aminoacil
Abnormal amino
acid (missense
energy
mutation)
Abnormal conclusion
Deletion
(Frameshift)
Ribosome
Transfer RNA
Amino acid
Processing
The processing abnorma
of the translation produ
(Proinsulin syndrome
Prepeptide cleavage
of membrane protein
Peptide cleavage, Glycosylation, Residue modification
Targetalization for membrane (1st-5th screening)
Conformation ← Chaperonin
Abnormal protein
Enzyme deficiency
Protein
Receptor deficiency
Transportor deficiency
Activity Structure
Processing Synthesis
of living
Peptide bond
Of inteprer of biological
body
material
product
Phenotype
Metabolic
abnormality
Dysfunction
Morphological
defect
Cell
Extraction
and
detection
method of
DNA
Heat annealing
Hybridization
(Molecular
hybridization)
Probe DNA
Radioactive phosphoric acid
or fluorescent dye
Base peculiar hydrogen
uniting formation
Denatured
protein
Phenol extraction,
Ethanol precipitation,
Protein-cutting enzyme
Double-stranded
DNA
Complementary
strand DNA
Alkali denaturation
or heat
denaturation
Autoradiography or
Fluorescence intensity
detection
T means U
when RNA
Single
Stranded
DNA
or RNA
Yasuo KAGAWA et at al. “Core, molecular
biology of human body” MARUZEN, 1997, p.20
Outline of Nutorigenomiccs
Environment
al factors
（Nutrient,
Function element,
Exercise）
DNA
：
Universal set
body in each
cell (ohm)
Genome
Transcript
RNA
： Transcriptome
Amount of ratio in
cell (profile)
Analysis
Gene multi type（SNP etc）
Difference
of cell
Genomics
*epigenetics
Gene expression profiling
(mRNA synthesis amount)
Transcriptomics
Proteomics
Translation
Protein
Individual
difference
： Proteome)
Protein appearance file
(enzyme and receptor,
etc.)
Vicissitude
Metabolite profile
(blood sugar, serum lipid,
and lactic acid, etc.)
Metabolites ： Metabolome
Diversity of action appearance
Metabolomics
bioinformatics
The mind and body's all activities
Lifestyle disease and aging
Yasuo KAGAWA. “Easy nourishment study”,
Kagawa Nutrition Publishing, 2006, p.163.
Lifestyle-related diseases prevention and mongoloid gene polymorphism
Appearance of disease and obesity of lifestyle disease
Mongoloid hunger
resistant gene multi type
Non-esterified
fatty acid
rise in blood
Hyperlipemia
Oxidation Ripo
protein
Genetic
factor
Lifestyle related
factor
Obesity
Insulin
resistance
Abnormal
glucose
tolerance
Globalization of
lifestyle of Corcasoid
hyperinsulinemia
Hypertension
Salt collect.
Sympathetic
nerve tension
festyle disease being found for gene related to appearance of diseas
Cancer
Hypertension
Obesity
C type of CYP1A1, etc
T type of Angiotensinogen, etc
Arg type of β Adrenaline receptor
Diabetics Uncoupling protein 3 (UCP 3) etc
Alzheimer type dementia
Apo E4 type, etc
Obesity factor
Monobasic multi type
Excess nutrient
Decrease in amount
of body activity
Tryptophane
β3 adrenaline receptor
Mutation
Amount of
intake
energy
Amount of
consumption
energy
Arginine
Life style factor
Obesity
Hereditary
determinant
Amount of metabolizing at rest and
β3 adrenaline receptor multi type
Kagawa Nutrition University
Students:175
(Average age 21)
Attendance lecture in Nutrition clinic
(KAGAWA Nutrition University) : 127
(kcal/day)
(Average age 50)
2000
P<0.01
NS
1500
1000
500
R/W
W/W
0
R/W
W/W
Source ： Prof. Kazuhiro UENISHI （Nutrition physiology, KAGAWA Nutrition University）
Obesity gene multi type in Nutrition clinic (KAGAWA
Nutrition University)
Receptor of not enzyme but biomembrane and multi type of transportation body
①β3 Adrenaline receptor
（β3AR）Trp64Arg
② uncoupling protein ２
（UCP2）45bp
insertion/deletion
③ uncoupling protein ３
（UCP3)C-55T
β3AR
β3AR
UCP2
UCP1
White adipocyte
Brown adipocyte
β2AR
UCP3
Both film proteins
concerning energy
transduction
Non-esterified
fatty acid
Frame muscle cell
Increase and decrease of amount of metabolizing of Japanese obesity gene
multi type at frequency and rest. There are a lot of multi types of the receptor
and the transportation body, and a multi type of the enzyme is few
Name of gene
The gene
multi type
remainder
radical and
position
Difference of amount
of resting metabolism
Kcal/a day
β3-AR
Trp64Arg
-200 (Arg aryl)
26％
β2-AR
Arg16Gly
+300 (Gly aryl)
16％
UCP1
a-3826g
-100 (G aryl)
40％
UCP2
Insert/Del
-200 (Loss)
35%
UCP3
c-55t
-100 (t aryl)
63%
Kir6.2
Glu23Lys
+100 (Lys aryl)
41%
LEPR
Gln233Arg
-100 (Arg aryl)
85%
RAGE
g1704t
-350 (t aryl)
14%
MTP
g-493t
-100 (t aryl)
21%
Frequency of aryl on
Japanese ％
Toshihide YOSHIDA,「Obesity treatment」, Available from
<http://metab.kuhp.kyoto-u.ac.jp/IKAI/report/no8.html>, (accessed
2007-12-11)
Racial difference of gene concerning nourishmen
Caucasian
Japanese
Amount of energy place
main point
Type of energy
consumption of large
amount
Type of
tolerance hunger
Alcohol metabolism
Strong
Weak
Farming culture
Stock raising
Rice farming
Multi type
concerned energy
Milk tolerance
The Japanese develops diabetes easily because of slight obesity.
The insulin secretion is few
Comparison of Japan-US diabetic patients
Rate of obesity
Japan
Insulin immunity
US
US
Japan
Fasting glucose
It is a big difference. the condition physiology and the expression type
SOCS2(supressor of cytokine signaling 2) difference of multi type gene
When the number of risk factor possession exceeds three, Metaboric
syndrome becomes 31 dangerous times the healthy individual
Risk is not mere addition
Appearance disease
odds rate
Nu m be r o f r isk fac t o r po sse sio n an d
35 appe ar an c e dise ase o dds r at e
30
25
20
15
10
5
0
Appearance disease
発症ｵｯｽﾞ比
Odds rate
0
1
2
3～4
Number of risk factor possesion
Risk factor
・Obesity
・hypertension
・High levels of
sugar
・Hyperlipemia
Kidney disease and losing sight can be prevented
by meal and exercise even
due to diabetic by the gene polymorphism
Data after it passes of 20 years or more of attending a lecture
Normal value of blood sugar
Diabetics and abnormal glucose tolerance
Adiponectin
Adiponectin
Keiko YANAGISAWA, Sayuri AIDA, Yasuo KAGAWA et at al
(Nutrition Clinic, Kagawa nutrition university)
Frequency of aryl of gene polymorphism
that promotes hypertension
α adducin
Ｔrp460
Angiotensinogen
Ｔ235
81
Japanese
Caucasian
57
Japanese
45
(Ishikawa, Hypertension
2001)
Caucasi15
an
(Ishikawa, Am J Hypertens
1998)
G proteinβ３（Na-H pumpﾟ）
Aldosterone synthase
Ｔ825
Ｔ-344
69
Japanes
e
Caucasi
an
50
(Tsujita, Hypertens Res 2001)
（unit：％）
Japanes
e
Caucasi 25
an
52
(Ishikawa, Am J Hypertens
2000)
One nitric oxide synthetic enzyme gene T786C multi type doesn't become
hypertension in case of the salt intake 11.7g or less/a day either
150
145
140
135
TT type
TC/CC type
130
TC/CC type that 17%
of 281 Japanese of
average age 45 year
becomes high blood
pressure easily
125
120
115
<7.5g
7.5-9.2g
9.2-11.7g
>11,7g
Miyaki. K. et al. “Salt Intake Affects the Relation Between Hypertension
and the T-786C Polymorphism in the Endothelial Nitric Oxide Synthase
Gene” Am J. Hypertension. 18(12), 2005, 1556-62
Hypertension appearance of disease rate and Angeotenshinorgen
gene polymorphism after three years intervention examinations
50
45 44
Incidence rate of
hypertension (%)
40
41
32
28
30
36
32
25
20
10
s
os
tl
gh
ei
W
di
so
wLo
On
ly
ob
se
rv
um
at
di
io
n
et
0
32
ＴＴ type
ＴＭ type
ＭＭ type
Obesity level (BMI) is ameliorable in no administering even if there
is a gene polymorphism related to four kinds of obesitys in the
guidance of the nutritional clinic
β3AR
（㎏/m2）
35.0
30.0
25.0
ns
p＜
26.4
-1.7
p＜
Wild
type
野生型群（n=91）
25.0
Mutation
変異型群（n=56）
type
UCP3
35.0
30.0
-1.7
25.5 23.9
24.6
20.0
（㎏/m2）
（㎏/m2）
ns
p＜
-1.8
26.1 24.4
-1.7
p＜
25.9
20.0
Wild
type
野生型群（n=64）
-1.2
35.0
-1.8
30.0
-2.4
25.0
-3
20.0
（㎏/m2）
-1.8
30.0
-2.4
25.0
-1.7
26.2 24.5
-1.7
p＜
25.5 23.9
Mutation
変異型群（n=42）
type
-1.7
p＜
0.0001
25.8 24.1
20.0
野生型群（n=59）
Wild
type
Amount of
change
-1.8
-2.4
FABP2
ns
24.2
After
lecture
-1.2
p＜
（㎏/m2）
35.0
（㎏/m2）
ns
Wild
type
野生型群（n=105）
-1.2
-3.0
Mutation
変異型群（n=83）
type
Before
lecture
UCP2
（㎏/m2）
-3.0
（㎏/m2）
-1.2
-1.7
p＜
26.1 24.4
-1.8
-2.4
-3.0
Mutation
変異型群（n=86）
type
After attending vs before a lecture is attended, the order
authorization with the sign and wild type group vs mutation type
group of Wilcoxon are U authorization of Mann-Whitney
Serum lipid improvement of both of escape after movement is
guided of nourishment of deficiency/deficient this type zygotic
mutation type of post protein 2
(mg/dl)
260
Total cholesterol
p=0.0007
p=0.0005
p<0.0075
(mg/dl)
p=0.0417
p<0.0001
115±48
241±53
240
130
Neutral fat
110
p<0.0001
p<0.0001
97±42
225±46
90
220
210±36
80±25
75±25
200
180
70
197±36
50
Before after
Wild group
(n=105）
Before after
Mutation type group
（n=42）
Before after
Wild group
（n=94）
Before after
Mutation type group
（n=34）
The Heart Disease and diabetes increasing suddenly by the
change to Western Europe lifestyle also in Thailand
During this 15 years:
Heart diseases x 5.1
Diabetes x 7.5
Cancer x 1.3
Heart
disease
Diabetes
Cancer
Thailand Health Profile 2000
The gene multi type frequency between Asians is similar
(By the research of “Kagawa Nutrition University High-tech research Center”
Okinawa (n=100)
PPARg2
LEPR ex6
Apo E
AGT M235T
2
98
11
2
AGT a-20c
b3AR
LEPR ex14
4 26
7 30
63
52
42
25
56
46
19
40
70
14
25 5
95
5
31
25
36
66
81
90
40
31 3
18 1
91
7
88
96
69
91
99
58
12 4
51
8 1
86
7 35
68
2 12
73
56
9
12 2
71
12 20
36
Mongol (n=252)
96
326
81
3
6
13
70
7 7
91
Palau (n=118)
94
6
89
UCP2
UCP3p
Thai (n=212)
81
41
27
3
15
41
52
69
4
45
14
30 1
72
26 2
9
65
33 2
1
71
27 2
Lifestyle disease and mongoloid receptivity gene
A
Mongoloid receptivity gene
B
Lipid, salt, sake, milk, movement, stress, and medicine
Action alternately
Appearance of disease
The agreement with the genetic test has increased overwhelmingly
as for the public opinion
Asahi Newspaper, March 12, 2006 morning newspaper
The Ministry of Education, Culture, Sports, Science and Technology specific area research
Information on the gene was considerably established.
(The percentage of those to whom the person who doesn't
know DNA understands 1% and the meaning is 55%. )
It was answered that the genomic study applied to the
medical treatment agreed by 70%, was opposite 1%, and it
was not able to be said that 29% was either.
The percentage of those who had answered that it wanted
to receive the genetic test to judge the easiness of the
medicine to be effective was 66%. It was a positive
response to apply the result to the medical treatment
(It questions about 4,000 general people in Japan, 2005.11)
The person of 73% hopes for the genetic test
Do you want to receive the genetic test?
I want to receive
it by all means.
I want to receive
it somewhat.
I do not want
to receive it.
I do not want
never to receive it
The Ministry of Economy, Trade
and Industry:
New health enhancement service
investigation with genome base
(February, 2006)
Because the resistance power strengthens economically advantageously
as for a saving gene multi type by an appropriate lifestyle guidance, too it
is ethical to notify a multi type
A multi type is diversity in the normal person group, and it is not
sick. Arg multi type of the β3 adrenaline receptor of the saving
gene can be ..200kcal.. few during a day. General food is
1kcal=1 yen, and the possibility of the living at the disaster is
high in one home. the holder of the saving saving gene during
360,000 yen/year
Because it is notified that it is a holder of the saving gene, and is
prevented the lifestyle disease as well as a general person if
guidance is received, it is not disadvantageous.
It is misunderstood to have advertised that discrimination
happens because it is disadvantageous the saving gene.
Because the saving gene is inspected, and the notification is
profitable to prevent the lifestyle disease, the report that fuels
opposite and the uneasiness to the genetic test is unethical.
I want to promote checkup to a possible genetic test and the
guidance of the treatment prevention
Patient
Me
Gene therapy (the first generation)
to fatal disease (terminal cancer etc.)
Patient
Me
Gene therapy to quality decrease (the
second generation) in important life
Patient
Me
Legal promotion of whole nation's
genetic test in Iceland etc
Patient
Me
Gene therapy transmitted by
descendant like mitochondria import in
the United States.
Patient
Me
Freedom of gene manipulation that
improves able-bodied person's mind and
body's ability and features, etc
○
×
○
×
Others
Others
Approval or disapproval
of ethics of gene medicine
（Medical student's result of the survey）
Ratio of cultivation area of the world of genetically
modified agricultural products in the world
(Million ha)
160
Non genetically modified
Genetically modified
140
120
100
80
60
40
20
0
55％
Soybean
21％
16％
Cotton
Colza
11％
Corn