Lecture 11 Gene and nutrition Obesity HyperlipemiaHypertension Oxidation Ripo protein Non-esterified...
-
Upload
ralf-holmes -
Category
Documents
-
view
214 -
download
0
Transcript of Lecture 11 Gene and nutrition Obesity HyperlipemiaHypertension Oxidation Ripo protein Non-esterified...
Lecture 11 Gene and nutrition
Obesity
Hyperlipemia Hypertension
Oxidation Ripo protein
Non-esterified fatty acid
rise in bloodhyperinsulinemia
Insulinresistance
Abnormal glucose
tolerance
Salt collect.Sympathetic nerve tension
Geneticfactor
Lifestyle relatedfactor
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
Hydrogen bond
G-C :3
A-T :2
Hydrogen bond
Single-standardDNA
Double-standardDNAPhosphoric
acid
DNA of parents cellDNA of
Child cellDivision
Direction of DNA strand
Gu
an
ine
Cy
tos
ine
Gu
an
ine
Cy
tos
ine
Cy
tos
ine
Gu
an
ine
Th
ym
in A
de
nin
e
Base
Ad
enin
e
Nu
cleotid
e
Yasuo KAGAWA et at al. “Core, molecular biology of human body” MARUZEN, 1997, p.2
The corresponding bases are united
It dissociates into single stranded DNA
Complementary Chain DNA against up
Pentose
Pentose
Base
Phosphoricacid
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
Statistical,
significant difference
Identical twin
( Men62 Women63 )
Homosexual fraternal twins
( Men86 Women92 )
p value
BMIBlood sugar rise for
120 minutes
Systolic pressureDiastolic blood pressure
Value of HDL cholesterol
0.68
0.52
0.55
0.47
0.61
0.28
0.26
0.17
0.07
0.26
<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
Men Women
Hyperlipemia(To Cerebral infarction
Cardiac infarction)
Hyperlipemia(To Cerebral infarction
Cardiac infarction)
Abnormal glucose
Tolerance(To diabetics)
Abnormal glucose
Tolerance(To diabetics)
Fre
qu
ency
per 1961 per 1961 Kyushu University the second internal medicine department Hisayama laboratory
Hyperlipemia:Total cholesterol
Comparison of 3 groups (40 or more) in Hisayama-machiAge
adjustmentperson
Relation between strength to alcohol and gene
Lysine
Lysine ThreonineThreonineGlutamic
acidValin
Normal type
Amino acidOf enzyme
Deletion form
single nucleotide
polymorphism
From father from mother
Strong Normal type / Normal type
Middle Deletion form / Normal type
Weak Deletion form /Deletion form
Base
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
Tohoku
Okinawa
gene
Northkyushu
Kanto
Shikoku
Hokkaido
South kyushu
Chugoku
Hokuriku
Kinki Chubu
frequency
HokkaidoTohoku
KantoChubu
HokurikuKinki
ChugokuNorth
Kyushu
ShikokuSouth
Kyushu
Amount of Alcohol consumption
Ethanol
Each prefecture investigated for 5000 Japanese or more in total
Year/person)
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
loss5.A passive, joint character: Guidance politely :: The SS type of
SerotoninT. 6.Folic acid and Epijeneticcs: Acknowledgment syndrome and cerebral infarction: TT type of MTHFR7.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 type9.Haplotype of mitochondria: New mongoloid feature
DNA reproductionRNA transcript
Protein translation
polymerase
ProteinRibosome Amino acid
Translation
Change of nucleotide sequence
Processing
Yasuo KAGAWA et at al. “Core, molecular biology of human body” MARUZEN, 1997, p.16
Peptide bondProcessing Of inteprer
product
Transfer RNA
DNA
Disease and gene information
Gene type
Aminoacil
Addition (Cap, Poly A)
Splicing
Synthesis of biological
material
Activity Structureof living
body
Reaction ofS period
(DNA Polymerase α)
Messenger RNA
Synthesis protein (Start, Extension, Conclusion)
The processing abnormality of the translation product
(Proinsulin syndrome)Prepeptide cleavage of membrane protein
Repli-cation
Trans-cription
Abnormal regulationOf expression
(Steroid hormone action, etc)Processing abnormal
Of the translation product(Thalassemia, etc )
energy
(Mutation)
Abnormal aminoacid (missense
mutation)Abnormal conclusion
Deletion (Frameshift)
Chromosome)
Metabolic abnormalityDysfunctionMorphological defect
Abnormal proteinEnzyme deficiencyReceptor deficiency
Transportor deficiency
Peptide bond
Conformation ← Chaperonin
Peptide cleavage, Glycosylation, Residue modificationTargetalization for membrane (1st-5th screening)
Self prolification
Phenotype
Extraction and
detection method of
DNA
Yasuo KAGAWA et at al. “Core, molecular biology of human body” MARUZEN, 1997, p.20
Double-strandedDNA
Autoradiography orFluorescence intensity
detection
Denatured protein
Cell
Heat annealingHybridization(Molecular hybridization)
Phenol extraction, Ethanol precipitation, Protein-cutting enzyme
SingleStranded
DNAor RNA
Complementary strand DNA
Alkali denaturationor heat
denaturation T means Uwhen RNA
Probe DNA Radioactive phosphoric acid
or fluorescent dye
Base peculiar hydrogenuniting formation
Environmental factors( Nutrient, Function element, Exercise )
Universal set body in each cell (ohm)
Amount of ratio in cell (profile) Analysis
DNA : Genome
Gene multi type ( SNP etc )
Individual difference
Genomics
Transcript
RNA : Transcriptome
Gene expression profiling
(mRNA synthesis amount) Transcriptomics
Proteomics
Metabolomics
Translation
Protein : 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
The mind and body's all activitiesLifestyle disease and aging
*epigeneticsDifference of cell
bioinformatics
Outline of Nutorigenomiccs
Yasuo KAGAWA. “Easy nourishment study”, Kag
awa Nutrition Publishing, 2006, p.163.
Obesity
Hyperlipemia Hypertension
Oxidation Ripo protein
Non-esterified fatty acid
rise in bloodhyperinsulinemia
Insulinresistance
Abnormal glucose
tolerance
Salt collect.Sympathetic nerve tension
Geneticfactor
Lifestyle relatedfactor
Lifestyle-related diseases prevention and mongoloid gene polymorphism
Appearance of disease and obesity of lifestyle disease
Mongoloid hunger resistant gene multi type
Globalization of lifestyle of Corcasoid
Cancer
Hypertension
Obesity
Diabetics
Alzheimer type dementia
Lifestyle disease being found for gene related to appearance of disease
C type of CYP1A1, etc
T type of Angiotensinogen, etc
Arg type of β Adrenaline receptor
Apo E4 type, etc
Uncoupling protein 3 (UCP 3) etc
Obesity factor
ObesityLife style factor Hereditary determinant
Excess nutrient
Monobasic multi type
Tryptophane
Arginine
Decrease in amount of body activity
β3 adrenaline receptor
Mutation
Amount of consumption
energy
Amount of intake energy
Amount of metabolizing at rest and
β3 adrenaline receptor multi type
R/W W/W0
500
1000
1500
2000
(kcal/day)
P<0.01
R/W W/W
Kagawa Nutrition University
Students:175
Attendance lecture in Nutrition clinic(KAGAWA Nutrition University) : 127
(Average age 21) (Average age 50)
NS
Source : Prof. Kazuhiro UENISHI ( Nutrition physiology, KAGAWA Nutrition University )
Obesity gene multi type in Nutrition clinic (KAGAWA NutriObesity gene multi type in Nutrition clinic (KAGAWA Nutrition University)tion University)
Receptor of not enzyme but biomembrane and multi type of transportation bodyReceptor 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
White adipocyte
β3AR
UCP2
β3AR
Brown adipocyte
UCP1
Frame muscle cell
UCP3
Non-esterified
fatty acid
β2AR
Both film proteins concerning energy transduction
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 metabolismKcal/a day
Frequency of aryl on
Japanese %
β3-AR Trp64Arg -200 (Arg aryl) 26 %β2-AR Arg16Gly +300 (Gly aryl) 16 %UCP1 a-3826g -100 (G aryl) 40 %
UCP2Insert/Del
-200 (Loss) 35%
UCP3 c-55t -100 (t aryl) 63%
Kir6.2 Glu23Lys +100 (Lys aryl) 41%
LEPRGln233Arg
-100 (Arg aryl) 85%
RAGE g1704t -350 (t aryl) 14%
MTP g-493t -100 (t aryl) 21%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 nourishment
Amount of energy place main point
Milk tolerance
Alcohol metabolism
Farming culture
Caucasian
Strong
Multi type concerned energy
Japanese
Type of tolerance hunger
Weak
Rice farmingStock raising
Type of energy consumption of large
amount
SOCS2(supressor of cytokine signaling 2) difference of multi type gene
The Japanese develops diabetes easily because of slight obesity. The insulin secretion is few
Comparison of Japan-US diabetic patients
Rate of obesity Insulin immunity
Japan
Japan
USUS
Fasting glucose
It is a big difference. the condition physiology and the expression type
When the number of risk factor possession exceeds three, Metaboric syndrome becomes 31 dangerous times the healthy individual
Number of risk factor possesion andappearance disease odds rate
05
101520253035
0 1 2 3 4~Number of risk factor possesion
App
eara
nce
dise
ase
odds
rat
e 発症オッス 比゙
Risk factor・ Obesity・ hypertension・ High levels of sugar・ Hyperlipemia
Risk is not mere addition
Appearance diseaseOdds rate
Kidney disease and losing sight can be prevented by meal and exercise even
due to diabetic by the gene polymorphism
Adiponectin
Adiponectin
Normal value of blood sugar Diabetics and abnormal glucose tolerance
Data after it passes of 20 years or more of attending a lecture
Keiko YANAGISAWA, Sayuri AIDA, Yasuo KAGAWA et at al (Nutrition Clinic, Kagawa nutrition university)
Frequency of aryl of gene polymorphism
that promotes hypertension
45
81Japanese
Caucasian
Angiotensinogen
T 235
50
69Japanese
Caucasian
Aldosterone synthase T -344
25
52Japanese
Caucasian
G proteinβ 3( Na-H pump )゚ T 825
15
57Japanese
Caucasian
α adducin T rp460
(Ishikawa, Hypertension 2001)
(Ishikawa, Am J Hypertens 1998)
(Tsujita, Hypertens Res 2001)
(Ishikawa, Am J Hypertens 2000)
( unit :%)
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
115
120
125
130
135
140
145
150
<7.5g 7.5-9.2g 9.2-11.7g >11,7g
TT typeTC/ CC type
TC/CC type that 17% of 281 Japanese of
average age 45 year becomes high blood
pressure easily
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
45
2825
44
3236
32
41
32
0
10
20
30
40
50 typeTT typeTM typeMMIn
ciden
ce rate of
hyp
ertensio
n (%
)
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
26.4 25.524.6 23.9
- 1.7 - 1.7
20.0
25.0
30.0
35.0
-3
-2.4
-1.8
-1.2
p<p<
26.2 25.524.5 23.9
- 1.7 - 1.7
20.0
25.0
30.0
35.0
-3.0
-2.4
-1.8
-1.2
p< p<
26.1 25.924.4 24.2
- 1.8 - 1.7
20.0
25.0
30.0
35.0
-3.0
-2.4
-1.8
-1.2
p< p<
25.8 26.124.1 24.4
- 1.7 - 1.7
20.0
25.0
30.0
35.0
-3.0
-2.4
-1.8
-1.2
p<0.0001
p<
ns
β3AR
野生型群( n=91 )変異型群( n=56 )
ns
UCP2
野生型群( n=105 ) 変異型群( n=42 )
変異型群( n=83 )野生型群( n=64 )
nsnsUCP3 FABP2
野生型群( n=59 ) 変異型群( n=86 )
(㎏ /m2 ) (㎏ /m2 )
(㎏ /m2 ) (㎏ /m2 )
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
Beforelecture
Afterlecture
(㎏ /m2 )
(㎏ /m2 )
(㎏ /m2 )
(㎏ /m2 )
Amount ofchange
Wild typeMutation
typeWild type
Wild typeWild typeMutation
type
Mutation type
Mutation type
180
200
220
240
260
Before after Before after
Wild group(n=105 )
Mutation type group ( n=42 )
Total cholesterol
50
70
90
110
130
Neutral fat
Before after Before after
Wild group( n=94 )
Mutation type group
( n=34 )
(mg/dl) (mg/dl)
210±36
197±36
241±53
225±46 97±42
75±25
115±48
80±25
p=0.0007p=0.0005
p=0.0417p<0.0001
p<0.0001
p<0.0075
p<0.0001
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
Thailand Health Profile 2000
During this 15 years:Heart diseases x 5.1Diabetes x 7.5Diabetes x 7.5Cancer x 1.3
DiabetesDiabetes
Heart disease
Cancer
The Heart Disease and diabetes increasing suddenly by the The Heart Disease and diabetes increasing suddenly by the change to Western Europe lifestyle also in Thailandchange to Western Europe lifestyle also in Thailand
95
70
46
25
7
25
40
56
52
30
91
11
5
14
19
6
63
7
89
98
42
2
5
2
Okinawa (n=100)
90
81
66
56
25
31
36
73
81
8
31
12
70
94
3
7
4
36
26
18
9
6
2
1
3
1
Thai (n=212)
99
91
69
12
9
30
96
88
40
68
26
51
12
71
96
9
1
20
3
1
1
3
3
1
Palau (n=118)PPAR2
LEPR ex6
Apo E
AGT M235T
AGT a-20c
UCP2
UCP3p
3AR
LEPR ex14 71
65
72
27
33
45
69
41
81
35
52
15
58
86
7
41
4
7
12
26
27
2
4
14
2
2
2
Mongol (n=252)
The gene multi type frequency between Asians is similarThe gene multi type frequency between Asians is similar(By the research of “Kagawa Nutrition University High-tech research Center”(By the research of “Kagawa Nutrition University High-tech research Center”
Mongoloid receptivity gene Lipid, salt, sake, milk, movement, stress, and medicine
Lifestyle disease and mongoloid receptivity gene
Action alternately Appearance of diseaseB
A
The agreement with the genetic test has increased overwhelmingly as for the public opinionAsahi Newspaper, March 12, 2006 morning newspaperThe 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 themedical treatment agreed by 70%, was opposite 1%, and itwas not able to be said that 29% was either. The percentage of those who had answered that it wantedto receive the genetic test to judge the easiness of themedicine to be effective was 66%. It was a positiveresponse 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
The Ministry of Economy, Trade and Industry:New health enhancement service investigation with genome base
(February, 2006)
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
Do you want to receive the genetic test?
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
Approval or disapproval of ethics of gene medicine
Patient MeGene therapy (the first generation) to fatal disease (terminal cancer etc.)
Patient MeGene therapy to quality decrease (the second generation) in important life
Patient Me
Legal promotion of whole nation's genetic test in Iceland etc
Patient MeGene therapy transmitted by descendant like mitochondria import in the United States.
Patient MeFreedom of gene manipulation that improves able-bodied person's mind and body's ability and features, etc
○×
Others
○×
Others
( Medical student's result of the survey )
Ratio of cultivation area of the world of genetically modified agricultural products in the world
0
20
40
60
80
100
120
140
160
Non genetically modifiedGenetically modified
Soybean Cotton Colza Corn55%
21%
16%
11%
(Million ha)