SNPs

Question 1

What is a “SNP”?

Answer 1

Single = One
Nucleotide= Base + Sugar + Phosphate
Polymorphism = Alteration

The most common type of genetic variation in humans and are responsible in part for the diversity among individuals. To be classified as a SNP, change must be present in at least 1% of the general pop.

Each SNP represents a change in a single DNA building block (called a nucleotide) - remember the 4 nucleotides are A, G, C, T that occur in many combos in our DNA to make up genes - a SNP is an alteration of one of these nucleotides

SNPS are genetic & can be passed down through families. Having a SNP doesn’t mean its active ad functioning - life, food, environmental exposures, stressors, etc. are all things that can express SNPs

They code for faster or slower enzymes & solution is sometimes to increase that nutrient cofactor to support the enzyme or make other related dietary lifestyle changes

Question 2

CYP1A2 function, difference between slow & fast enzyme activity

Answer 2

Over 90% of caffeine metab is carried out by this enzyme.

fast metabolizers (fast enzyme activity ) can enjoy the health components and benefits with coffee and/or caffeine including (polyphenols, bitter compounds to support liver & gallbladder, lower risk of CVD and stroke @ reasonable dose)

Those that are slow metabolizers won’t have same benefits and will have increased risk of negative outcomes instead if they overcome; odds of having a heart attack increase if 2-4+ cups of coffee are drank/day, decreased athletic performance, increased risk of hypertension

Question 3

CYP34A - function, inhibitors and inducers

Answer 3

Enzyme encoded by this gene is found mainly in liver and intestines & plays large role in med metabolism “CYP3A4 is the one to watch 4, it handles the most meds @ the door”

Responsible for more than 65% of all meds & metabolizes vit D & testosterone

Inhibitors/antagonists = grapefruit, resveratrol, Quercetin = slow metabolism of med which keeps in body longer and increases risks of side effects

Inducer/agonist = SJW, glucocorticoids like NSAIDs (speeds up enzyme activity which speeds up med clearance making it less effective)

Question 4

CYP19A1 - function?

Answer 4

Aromatase/synthesis of estrogen

Question 5

VDR - what is it and what can variations affect?

Answer 5

The vitamin D receptor (VDR) encoded for by the gene VDR is the receptor for the bioactive form of vitamin D, calcitriol.

When vitamin D binds to VDR the receptor is activated and this initiates the expression of a protein called calbindin. Calbindin binds with calcium and greatly improves the efficiency of its absorption through the gut, and can also hold calcium in the blood for later use

Variations (SNPs) in VDR gene can affect:
- Vitamin D sensitivity
- Bone mineral density
- Risk of autoimmune diseases
- Cancer risk

Question 6

BCO1/BCMO1 - function?

Answer 6

Beta carotene conversion to active vitamin A

Question 7

MTHFR - encodes for enzyme that converts what to what?

Roles?

Answer 7

5,10-methylenetetrahydrofolate → 5-methyltetrahydrofolate (5-MTHF); This is the active, methylated form of folate used to convert homocysteine to methionine, a crucial step in the methylation cycle

roles - DNA/RNA synthesis and repair, Neurotransmitter production, Detoxification (via SAMe), Cardiovascular and mood health

Question 8

ACE - function and what happens if upregulated?

Answer 8

Salt sensitive hypertension; SNP occurs in the renin-angiotensin pathway:

In liver Angiotensinogen —> angiotensin I —ACE—-> angiotensin II, a vasocontributor that increases BP

NaCl increases ACE enzyme

If upregulated enzyme makes more angiotensin II = increase BP (~60% of people w/this SNP have salt sensitive HTN)

if no changes in enzyme speed, no reaction to salt - so if these people have HNT, a salt reduction diet (DASH) may not benefit

Question 9

APOE

Answer 9

APOE SNP referes to gene that codes apolipoprotein E (ApoE). ApoE helps to bind, transport, and breakdown fats (TGs & cholesterol) and can help to regulate inflammation

Many different types of variants within APOE

Question 10

Celiac disease risk gene

Answer 10

HLA-DQ2 & HLA-DQ8

Question 11

Slow caffeine metabolizers have a SNP in what enzyme? What happens if they drink 2+ cups of caffeine consistently?

Answer 11

C allele

Is they consume 2-4+ cups of coffee/day may have 35-60% increased risk of myocardial infarction (heart attack)

Experience reduced athletic performance with high intakes of caffeine

Caffeine more likely to contribute to anxiety, insomnia, and estrogen dominance if they over-consume

1 cup/day isn’t likely to cause these

Question 12

What are inhibitors and inducers of the function of the enzyme encoded by gene CYP3A4?

Answer 12

Inhibitors (antagonists) - grapefruit, Quercetin, resveratrol; inhibits CYP3A4’s action on statins.

Question 13

What nutrient is COMT dependent on? What phytonutrient slows down (inhibits) COMT? What would a nutrition intervention be for a COMT-AA-variant (slow) be?

Answer 13

Mg (also needs B6)

Quercetin

To avoid Quercetin which is usually used for mast cell stabilization; support Mg through food & supplement

Question 14

What variation in COMT is associated with increased risk for cancer in those who supplement which vitamin ___

Answer 14

Homozygous GG (fast, so lower dopamine d/t quick clearance) w/supplemental vit E

Question 15

APOA2

Answer 15

Saturated fat & obesity

Carriers of T allele (TT or TC), obesity isn’t as affected by saturated fat intake

CC homozygotes - presence of obesity dependent on how much sat fat they were eating; increased risk with sat fat intake about 22 g/day

Question 16

What is methylation? What does it affect? What can happen if methylation isn’t working properly

Answer 16

Adding of a methyl group to a molecule (carbon and 3 hydrogens) - adding a methyl group turns genes on or off

DNA repair and synthesis, detox of hormone and chemicals, energy production and metabolism, mental health (crucial for synthesizing neurotransmitters) and needed to turn some vitamins to their active forms

risk of cancer, aging, oxidative stress, mental health & mental illness, r/t neural tube defects & miscarriage, CVD

Question 17

What condition is increased w/high homocysteine? What condition is increased with lower folate? What downregulated enzyme/gene is this related to?

Answer 17

CVD, stroke, heart attack

Neutral tube defects, miscarriage

MTHFR TT or CT

Question 18

Define each:

Methylation
Homocysteine
MTFHR
Transsulfuration

Answer 18

1. Process of adding a methyl group (CH3) which impacts DNA expression, detox, mental health & catecholemines
2. Inflammatory in excess, can increase risk of heart disease, requires b12 & b9 (F-MTHF) to convert to methionine; can use back up pathways w/adequate zinc, choline, and betaine; can use b6 to enter transsulfuration
3. MTFHR influences MTHFR enzyme activity and folate metabolism. Impacts speed at which folate is converted to 5-MTHF, which is the form that enters the methylation pathway
4. Transsulfuration - connects to methylation pathway by homocysteine —> cysteine; requires b6; crucial for sulfur metabolism (& therefore taurine & bile acids) & redox balance in cells (glutathione & ox stress)

Question 19

MTNR18 & interventions?

Answer 19

Function: Binds melatonin and regulates circadian rhythm and insulin secretion

Prolonged melatonin production/morning insulin suppression so T2D risk

Interventions = very low carb breakfast/morning fasting. Evening melatonin supplementation or late-night eating might worsen glycemic control in those with risk alleles

Question 20

Phenylketonuria (PKU) - what is it and what happens, what would be an intervention?

Answer 20

Inborn error of metab - inherited disease where body cannot metabolize amino acid phenylalanine (typically phenylalanine is converted to tyrosine) so phenylalanine builds which is toxic to brain and can result in severe intellectual disability (d/t reduction in tyrosine which is precursor to dopamine)

Intervention = carefully controlled low protein phenylalanine restricted diet (avoid aspartame, phenylalanine is a component of aspartame)

Question 21

What is maple syrup urine disease (MSUD), what happens and what’s an intervention?

Answer 21

Inborn error of metab - autosomal recessive metabolic disorder affecting BCAA

Typically branched chain alpha keto acid dehydrogenase enzyme metabolizes BCAAs (catalyzed but B1), but it doesn’t work so BCAAs begin to rise in blood (often w/in few hours of birth) and can lead to neurological dysfunction

Intervention = low protein where 3 BCAAs (valine, leucine ,isoleucine) are VERY controlled; in some cases B1 is supplemented if case is mild

Question 22

Galactosemia? Intervention?

Answer 22

Body can’t metabolize galactose (monosaccharide found in lactose). Enzymes that are supposed to work but don’t are GALT, GALK, GALE - galactose build and can be converted to galactitol (sugar alcohol that’s toxic)

Strict lactose free and galactose free diet

Question 23

Fructosemia? Intervention?

Answer 23

Hereditary fructose intolerance (different than fructose malabsorption)

Fructose builds and damages liver & can be lethal

Intervention - low or fructose free diet, which also avoids/limits sucrose and sorbitol (sugar alcohol that body converts to fructose)

Question 24

Biotinidase deficiency? Intervention?

Answer 24

Inherited disorder in which the body is unable to recycle biotin d/t biotinidase enzyme not functioning properly so severe biotin deficiency

Intervention = biotin supp

Question 25

MCM6 & intervention

Answer 25

gene contains regulatory regions that control the expression of the LCT gene (which encodes lactase) Clinical Issue: Lactose intolerance if lactase non-persistence (lactase persistence = lactase production persists into adulthood; lactase persistence is the genetic mutation, not the default) T allele: associated with continued lactase production (lactase persistence). C allele: associated with reduced lactase production (lactase non-persistence) Nutritional Intervention: Limit lactose intake; consider lactase enzyme supplementation; monitor calcium/vitamin D intake intervetions - remove dairy or use lactase enzyme

Question 26

What % of the world has lactase non-persistence? What gene controls this?

Answer 26

lactase non-persistence is normal worldwide — in fact, about 65-70% of the global population has some degree of lactase decline after weaning MCM6

Question 27

Distinguish between primary lactose intolerance and secondary lactose intolerance

Answer 27

primary lactose intolerance = genetic, due to MCM6 SNP secondary lactose intolerance due to injury to intestinal lining, e.g., after celiac disease, infection

Question 28

What is the function of the LCT gene? What regulates LCT gene expression in adults?

Answer 28

Encodes the enzyme lactase for lactose digestion SNPs in MCM6 regulatory regions, not changes in LCT coding region itself

Question 29

What groups have the highest rates of lactose persistence (ability to digest lactose)?

Answer 29

found in northern europeans and arab ancestries

Question 30

APOE variants APOE2 APOE3 APOE4

Answer 30

APOE2 - may be protective against Alzheimer’s. Associated w/increased CV risk (T allele) - thought to bind less well with its receptors limiting clearance of dietary fat from blood increasing clot formation (shown to decrease LDL but increase TGs) APOE3 - the “neutral” form of APOE and most common; doesn’t increase or decrease Alz risk APOE4 - primary risk variant that’s closely associated w/increased Alz risk. One copy = 2-3x Alz risk, 2 copies = 12x risk; strongly linked to inflammation, oxidative stress. Makes lipid metab more difficult which may cause lipid build up, so keto diet may NOT be beneficial

Question 31

What reaction is catalyzed by the BHMT enzyme?

Answer 31

Homocysteine to methionine using betaine

Question 32

BHMT Gene: stands for? encodes enzyme for ____ Uses: ____ as methyl donor Converts: ____ ➔ ____ Supports alternative pathway to what? Clinical Tip: Defects = potential hyperhomocysteinemia → supplement with?

Answer 32

Betaine Homocysteine Methyltransferase; betaine-dependent methylation Betaine (Trimethylglycine) as methyl donor Converts: Homocysteine ➔ Methionine Supports → Alternative pathway to folate/B12-dependent methylation Clinical Tip → Defects = potential hyperhomocysteinemia → supplement with betaine, choline, zn

Question 33

CBS gene function, what SNP can lead to, and nutritional interventions

Answer 33

Function - CBS gene encodes the cystathionine β-synthase enzyme, which plays a central role in the transsulfuration pathway. Converts homocysteine to cystathionine, which eventually becomes cysteine — important for glutathione production SNP can cause -elevated homocysteine (a risk factor for cardiovascular disease, stroke, and neurodegeneration), reduced glutathione production, potential increase in ammonia levels, as CBS activity affects sulfur metabolism B6 if underfunctioning

Question 34

FTO - what is it?

Answer 34

Fat mass and obesity-associated protein (FTO) is an enzyme which interacts with RNA molecules and is thought to influence expression of proteins, it is encoded for by the FTO gene. FTO has been termed the “obesity gene” in popular culture due to a variety of studies which described and association between certain SNPs and increased body mass

Question 35

Neurotransmitters broken down by MAOA how MAOA activity level affects mood and behavior Nutritional cofactor support for MAOA Implications for clients with mood, ADHD, or anxiety disorders

Answer 35

MAOA encodes the monoamine oxidase A enzyme, which breaks down serotonin, norepinephrine, dopamine, melatonin This helps regulate mood, emotional response, stress tolerance, and sleep low-activity MAOA variants = reduced breakdown → higher neurotransmitter levels & can predispose individuals to ADHD, PTSD, anxiety, or aggression, especially under chronic stress. Cts may feel “wired but tired” and be sensitive to stimulants high activity variant = faster breakdown = lower baseline levels of serotonin/dopamine and potential mood instability; can be more prone to depression nutritional cofactors = B2

Question 36

PEMT - what is it, what is end substrate used for, and nutritional intervention for a SNP leading to impaired function?

Answer 36

PEMT encodes the PEMT enzyme, which converts phosphatidylethanolamine (PE) into phosphatidylcholine (PC) in the liver, using S-adenosylmethionine (SAMe) as a methyl donor. Phosphatidylcholine is critical for: cell membrane structure, lipid transport (via VLDL), liver fat metabolism, choline production, methylation recycling intervention = phosphatidylcholine, choline rich foods (egg yolk), and supporting methylation pathways (Mg, folate, b12, betaine/TMG)

Question 37

HMNT - what is it?

Answer 37

HNMT encodes the histamine N-methyltransferase enzyme, which breaks down histamine — primarily inside cells, especially in the central nervous system (CNS) and airways. It does so by methylating histamine, using SAMe as the methyl donor histamine is involved in - Histamine is involved in: immune response (allergies, inflammation), neurotransmission, gastric acid secretion, wakefulness/sleep regulation a SNP can reduce the enzyme’s ability to break down histamine → intracellular histamine buildup

Question 38

Difference between HMNT and DAO

Answer 38

HNMT is the primary histamine degradation pathway in the brain — unlike DAO, which works in the gut

Question 39

Intervention for SNP in HMNT

Answer 39

Methylation support is key: SAMe, Vitamin B12, Folate, Vitamin B6, Magnesium Avoid high-histamine foods if symptomatic Consider quercetin, vitamin C, and DAO enzymes (for gut-based support) Gut healing may also help reduce overall histamine load

Question 40

Briefly explain how a polymorphism in the PEMT gene may increase dietary choline needs.

Answer 40

A PEMT SNP can reduce endogenous production of phosphatidylcholine, making the body more reliant on dietary choline to maintain liver function, VLDL export, and methylation balance.

Question 41

Your client reports anxiety, insomnia, and sensitivity to fermented foods and red wine. Which gene would you consider relevant and what intervention might you recommend?

Answer 41

HNMT — impaired histamine breakdown in the CNS. Support with methylation cofactors (B12, folate, B6), and reduce dietary histamine load. Consider DAO support if GI involvement is suspected.

Question 42

Consequences of reduces MTHFR function?

Answer 42

Elevated homocysteine (↑ CVD, stroke, miscarriage risk Poor methylation → low SAMe, affecting: mood and mental health (↓ serotonin, dopamine synthesis), detoxification (esp. phase II liver function), estrogen metabolism, histamine clearance Risk of neural tube defects in pregnancy Increased sensitivity to synthetic folic acid

Question 43

Key nutrient cofactors to support MTHFR?

Answer 43

B2, B3, folate

Question 44

If a client reports adverse effects (like anxiety or restlessness) from high-catecholamine supplements (e.g., green tea extract, L-tyrosine, rhodiola), consider a ____ SNP as a possible root cause — especially if symptoms worsen with stress or stimulants

Answer 44

COMT - slow COMT would = slow clearance of catecholemines = build up of catecholemines and overstimulation/anxiety.

Question 45

In someone with slow COMT activity, what supplements could increase anxiety, racing thought, insomnia, overstimulation?

Answer 45

quercetin, high catecholemine supplements like green tea extract (EGCG is a COMT inhibitor), L-tyrosine, rhodiola

Question 46

T/F - VDR polymorphisms can affect vitamin D receptor sensitivity even if serum 25(OH)D levels are normal

Answer 46

true