Nutrition X Genes + Age Related Disease

Question 1

What does gene x environment interactions target

Answer 1

Disease pathways and prevention pathways eg antioxidants or immune system

Question 2

What are nutrients and the 2 types

Answer 2

Active chemicals in our diet
Macro- fat,carb,protein needed for energy and growth
Micro- vitamins and minerals for health

Question 3

What is the first known example of how diet impacted genes

Answer 3

Lactase tolerance through adaptive mutations in the gene

Appeared in Turkish farming cultures whcih then migrated to Northern Europe 80% now tolerant

Question 4

What dna repair mechanism seen to cause longevity so maybe is impaired during ageing

Answer 4

Parp

Question 5

Does ageing have set genes

Answer 5

No dependant on accumulative damage

Question 6

What is the free radical theory

Answer 6

Where rod builds up and accelerates senescence both by telomeric shortening and cellular senescence and also causes inflammation via nfkb and ap1 tf

Question 7

How does inflammation relate ageing to disease

Answer 7

Inflammation a big basis for a lot of chronic age diseases eg cvd and ra

Question 8

What does telomere shortening cause in return to further cause damage

Answer 8

Mt dysfunction through p53 activation which blocks pary coactivators

Question 9

What is the term called where removal of correct proteins not done during ageing

Answer 9

Loss of proteostasis

Question 10

How is ageing linked to the same common pathways of age related diseases

Answer 10

They show loss of mt function, loss of oxidative stress management , repair mechanisms, cellular maintenance and inflammatory problems

Question 11

What % of inter individual variations made up by snps

Answer 11

90%

Question 12

What 3 things do snps cause differences in

Answer 12

Variations in dietary requirements

Susceptibility to disease

Medication response

Question 13

What else do snps need because of their low or

Answer 13

Environment

Eg pnpla3 and obesity for nafld

Question 14

Explain how snps used to confer advantage now are detrimental

Answer 14

Different diets, pathogens etc

Used to have famine so developed snp for fat storage now detrimental

Some snps to fight pathogens now autoimmunity

Question 15

What is the difference between nutrifenomics and genetics

Answer 15

Genomics is how nutrients affect gene exp/protein exp. Looked at via transcriptomics and proteomics

Genetics is how our genes affect our response to nutrients and their effects on us

Question 16

Why are both looked at

Answer 16

For personalised nutritional advice

Question 17

What is the main advantage of a candidate approach to study snps

Answer 17

Small population so can match them.

And because only certain functional snps in known genes looked at can have additional tests like snp x nutrition tests

Question 18

What is the main disad

Answer 18

Only 1-20 snps looked at so missing out on viral info on other snp associations

Question 19

Why does a larger popn needed in pathway approach

Answer 19

More snps tested both known functionality and unknown in target genes

Need to maintain statistical power

Question 20

To reduce risk of false positives what needs to be done to the p value and why is this bad

Answer 20

Reduce the p value threshold, meaning it is hard to identify snps with small effects

Question 21

Using what technique in pathway eradicates the need for this

Answer 21

Tagsnps

As you’re testing less snps

Question 22

What sorts of tests can still be done in pathway but not in gwas

Answer 22

Snpxsnp and snpxnutrient interacfion

Question 23

How many snps tested in gwas

Answer 23

5 million because testing all snps not just in certain pathways

Question 24

What does this allow for

Answer 24

Identifying new gene/snp associations and new pathways

Question 25

What can’t be done in gwas which is in candidate and pathway

Answer 25

Matched controls and further tests

Question 26

What is an issue with genotyping Plato forms in gwas

Answer 26

Very westernised so don’t necessarily portray the LD and allele freq in other ethnicities

Question 27

Which 2 pathways have been studied via candidate approach for snp x nutrient interactions

Answer 27

Lipid metabolism (apoa1 x pufa) Bcmo1 x vit a/retinol

Question 28

What does apoa1 do

Answer 28

Lipid metabolism involvemnef Efflux of hdlc and transport to liver

Question 29

What does increased hdlc reduce risk of

Answer 29

Cvd

Question 30

Do snps in apoa1 cause changes in hdlc conc alone

Answer 30

No they need influence of pufa intake (polyunsaturated fatty acids from diet)

Question 31

A allele carriers usually have lower apoa1 and hdlc conc. how was this reversed in women (study)

Answer 31

Higher conc of pufa intake

Question 32

What did higher conc of pufa cause in gg carriers

Answer 32

Lowered hdlc conc so increase cvd risk

Question 33

What did lower conc for gg do

Answer 33

Increase hdlc in gg

Question 34

What is b carotene

Answer 34

A pro vitamin carotenoid (from plant/veg) Which is converted to vitamin A

Question 35

Which snp affects the availability of vitamin A in this pathway of conversion

Answer 35

Bcmo1

Question 36

Why is this an issue in vegans

Answer 36

Only source of vitamin a in diet is pro vit A carotenoids

Question 37

Why is vitamin A needed

Answer 37

Can cause night blindness and increased risk of infection as necessary for t lymphocyte proliferation Also needed for cell growth and differentiation

Question 38

Why is this a Bcmo1 snp x snp interaction

Answer 38

Because a double mutant in females caused greater loss of enzymatic activity

Question 39

What does bcmo concert b carotene into which was found in lower ratio in mutant females

Answer 39

Retinal

Question 40

What is folate

Answer 40

Naturally occurring folic acid (vit b9)

Question 41

What is it converted to for activity by mthfr

Answer 41

5- methyl thf

Question 42

What things is folate major for

Answer 42

Dna / rna synthesis / repair via nucleotide synthesis Methylation Detoxification of homocysteine hcy (cvd risk factor)

Question 43

Which congenital defect means folate supplementation recommended

Answer 43

Ntd

Question 44

What sorts of chronic diseases could folate deficiencies or the snp in folate metabolism cause

Answer 44

Cancers, cvd

Question 45

What enzyme converts folate to active 5-methyl thf

Answer 45

Mthfr

Question 46

How is hcy detoxified

Answer 46

Uses 5-methyl thf to remethylate it into methionine which is used to form SAM methyl donor

Question 47

What snp is in the mthfr

Answer 47

C677t

Question 48

What does it do

Answer 48

Reduces the activity of mthfr in 37C (body temp) if T allele carried

Question 49

What would carrying TT and also low folate intake do

Answer 49

V high hcy levels and low plasma folate = increased cvd risk

Question 50

How is it a diet x snp interaction

Answer 50

Folate intake will compensate and reduce levels of hcy in TT carriers

Question 51

What is the issue with higher folate

Answer 51

Can also cause cancer risks - eg maybe via methylation of tumour suppressors or by donating nucleotides for tumour cell growth

Question 52

Is there variations in snp frequency in diff populations

Answer 52

Yes, v low in african Americans but high in Asia and Hispanics

Question 53

Does TT impact on Ntd risk

Answer 53

Yes if mother is TT/has high hcy/low folate = Ntd risi

Question 54

Why is genotyping seen as important for therapy here and why is it difficult

Answer 54

TT carriers need highest supplementation of folate to return it back to normal levels Difficult because of that cancer risk

Question 55

During folate deficiency, what is incorporated into dna instead of thymidine which causes dna strand breaks and malignancy

Answer 55

Uracil

Question 56

Why would snps in mthfr be protective of this

Answer 56

Because they increase available 5,10 methylene thf for thymidine synthesis

Question 57

Under normal folate arguments how does it reduce cancer

Answer 57

Methylation of protooncogenez Purine and thymidine production for dna repair