SNPs Flashcards
What is a “SNP”?
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
CYP1A2 - which allele leads to reduced activity and what leads to sped activity? AA? CC? CA? What does this mean?
Over 90% of caffeine metab is carried out by this enzyme.
The C allele leads to reduced activity of this enzyme so…
AA = fast caffeine metabolizers
AC or CC = slow caffeine metabolizers
Those w/homozygous AA 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 with C allele may not receive 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, 14% decrease in athletic performance and increased risk of hypertension
CYP34A
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)
CYP19A1
Aromatase/synthesis of estrogen
VDR - what is it and what can variations affect?
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
BCO1/BCMO1
Beta carotene conversion to active vitamin A
MTHFR C677T & MTHFR A1298C
what variations cause lower enzyme activity? What would this lead to?
Detoxication and folate metabolism
MTHFR C677T results in 30-40% reduction in MTHFR enzyme activity (C/T). Homozygous T/T = 60-70% reduction in enzyme activity. CC = NO DOWNREGULATION
Heterozygous for only 1298 (A/C) has not been shown to affect overall enzyme activity; homozygous (C/C) results in 30-40% reduction in enzyme activity
With downregulated enzyme activity which limits methylation rxns in body = increased risk of high homocysteine and increased tendency for lower folate levels
COMT - what variations are fast, slow, and intermediate?
G/G
A/A
G/A
Detoxification & catecholamines - degrades dopamine, NE, and E. Also methylates estradiol
Fast COMT (G/G; Val/Val) = gets rid of dopamine more quickly = low levels of all 3 catecholemines (sx of low dopamine; may need more stimulation)
Slow COMT (A/A; Met/Met) = build up of dopamine (sx of high dopamine; over stimulated/may be more stress sensitive); also less efficient breakdown of estradiol so can lead to estrogen dom & related conditions
G/A (Val/Met) = intermediate
ACE
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
GA & AA version of ACE SNP = unregulated enzyme (makes more angiotensin II = increase BP (~60% of people w/this SNP have salt sensitive HTN)
GG version of ACE SNP = no changes in enzyme speed (no reaction to salt) - so if these people have HNT, a salt reduction diet (DASH) may not benefit
APOE
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
HLA-DQ2 & HLA-DQ8
Celiac disease risk
Slow caffeine metabolizers have what allele and what does this mean?
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
What are inhibitors and inducers of the function of the enzyme encoded by gee CYP3A4?
Inhibitors (antagonists) - grapefruit; inhibits CYP3A4’s action on statins.
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?
Mg
Quercetin
To avoid Quercetin which is usually used for mast cell stabilization; support Mg through food & supplement
What variation in COMT is associated with increased risk for cancer in those who supplement which vitamin ___
Homozygous GG (fast, so lower dopamine d/t quick clearance) w/supplemental vit E
APOA2
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
What is methylation? What does it affect?
Transfer of methyl groups (CH3)
DNA, detox, risk of cancer, aging, oxidative stress, mental health & mental illness, r/t neural tube defects & miscarriage, CVD
What condition is increased w/high homocysteine? What condition is increased with lower folate? What downregulated enzyme/gene is this related to?
CVD, stroke, heart attack
Neutral tube defects, miscarriage
MTHFR TT or CT
Define each:
Methylation
Homocysteine
MTFHR
Transsulfuration
- Process of adding a methyl group (CH2) which impacts DNA expression, detox, mental health & catecholemines
- 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
- 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
- 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)
MTNR18 & interventions?
Prolonged melatonin production/owning insulin suppression
Interventions = very low carb breakfast/morning fasting
Phenylketonuria (PKU) - what is it and what happens, what would be an intervention?
Inborn error of metab - inherited disease where body cannot metabolize amino acid phenylalanine (typically phenylalanine is converted to tyrosine) so phenylalanine but;D’s 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)
What is maple syrup urine disease (MSUD), what happens and what’s an intervention?
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 protein where 3 BCAAs (valine, leucine ,isoleucine) are VERY controlled; in some cases B1 is supplemented if case is mild
Galactosemia? Intervention?
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
Fructosemia? Intervention?
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
