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My genetics

elevated-riskYesterday evening I ran up to my computer and started clicking madly in every direction after I saw an email from 23andme.com alerting me that my genetic profile was ready. No methylation or detox information in sight but lots of other interesting things (see image on right). My risk of developing Parkinson’s or Alzheimer’s is below average – awesome! Maybe I will thrive into old age after chelating out the heavy metals.

It took me about 15 minutes just to dig up the website where people get their raw 23andme.com data interpreted automatically for methylation info. That is something called sterling’s app and it cost $20. Now I see there are probably a couple others namely Genetic Genie and Livewello. Anyhow, here are my results below. Guessing it will take weeks or months or longer for me to understand the key sections – detox, methylation and mitochondrial. Right now, I’m clueless.

Update: I’ve learned a lot since receiving my results and have posted the research below underneath the various results it applies to – hope this may help you evaluate your own genetics. Amazingly, 23andme identified my mother’s maiden name in the ancestry results. Actually, they show the top five relative surnames and the number one surname happens to be my mom’s maiden name! The other four names are also quite illustrious.

If you’re unfamiliar with basic genetics, there’s a primer below.

DETOX
Gene & Variation rsID # Risk Allele Your Alleles & Results
CYP1A1*2C A4889G rs1048943 C TT -/-
CYP1A1*4 C2453A rs1799814 T GG -/-
CYP1A2 C164A rs762551 C AC +/-
CYP1B1 L432V rs1056836 C CG +/-
CYP1B1 N453S rs1800440 C TT -/-
CYP1B1 R48G rs10012 C GG -/-
CYP2A6*2 A1799T rs1801272 T AA -/-
CYP2C19*17 rs12248560 T CC -/-
CYP2C9*2 C430T rs1799853 T CC -/-
CYP2C9*3 A1075C rs1057910 C AA -/-
CYP2D6 S486T rs1135840 G GG +/+
CYP2D6 T100C rs1065852 A GG -/-
CYP2D6 T2850C rs16947 A AA +/+
CYP2E1*1B G9896C rs2070676 G CC -/-
CYP2E1*4 A4768G rs6413419 A GG -/-
CYP3A4*1B rs2740574 C TT -/-
CYP3A4*3 M445T rs4986910 G AA -/-
CYPs are primarily membrane-associated proteins located either in the inner membrane of mitochondria or in the endoplasmic reticulum of cells. CYPs metabolize thousands of endogenous and exogenous chemicals. Some CYPs metabolize only one (or a very few) substrates, such as CYP19 (aromatase), while others may metabolize multiple substrates. Both of these characteristics account for their central importance in medicine. Cytochrome P450 enzymes are present in most tissues of the body, and play important roles in hormone synthesis and breakdown including estrogen and testosterone synthesis and metabolism, cholesterol synthesis, and vitamin D metabolism. Cytochrome P450 enzymes also function to metabolize potentially toxic compounds, including drugs and products of endogenous metabolism such as bilirubin, principally in the liver.

rs762551 (C) allele is a slow metabolizer or of certain substrates including caffeine which means I’m more stimulated by it than most people.

rs1056836 increases susceptibility to lung and breast cancer, blocks testosterone and inhibits mitochondrial function.

rs1135840 is involved in the metabolism of approximately 25% of all medications and most psych meds including antipsychotics and antidepressants.

GPX3 rs8177412 C TT -/-
GSTM1 rs12068997 T CC -/-
GSTM1 rs4147565 A GG -/-
GSTM1 rs4147567 G AA -/-
GSTM1 rs4147568 A TT -/-
GSTM1 rs1056806 T CC -/-
GSTM1 rs12562055 A TT -/-
GSTM1 rs2239892 G AA -/-
GSTP I105V rs1695 G AG +/-
GSTP1 A114V rs1138272 T CC -/-

GSTP genes encode the Glutathione S-transferase P enzyme. Glutathione S-transferases (GSTs) are a family of enzymes that play an important role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. Mutations here will increase your need for glutathione and importance of chelating out mercury.

rs1695 influences asthma risk.

NAT1 A560G(?) (R187Q) rs4986782 A GG -/-
NAT2 A803G (K268R) rs1208 G GG +/+
NAT2 C190T (R64W) rs1805158 T CC -/-
NAT2 G590A (R197Q) rs1799930 A GG -/-
NAT2 G857A (G286E) rs1799931 A GG -/-
NAT2 T341C (I114T) rs1801280 C CC +/+

NAT2 encodes N-acetyltransferases which are enzymes acting primarily in the liver to detoxify a large number of chemicals, including caffeine and several prescribed drugs. The NAT2 acetylation polymorphism is important because of its primary role in the activation and/or deactivation of many chemicals in the body’s environment, including those produced by cigarettes as well as aromatic amine and hydrazine drugs used medicinally. In turn, this can affect an individual’s cancer risk.

I have a particular combination of NAT2 polymorphisms – rs1801280 (C) + rs1208 (G) which makes me a ‘slow metabolizer’. In general, slow metabolizers have higher rates of certain types of cancer and are more susceptible to side effects from chemicals (known as MCS) metabolized by NAT2.

SOD2 rs2758331 A AA +/+
SOD2 rs2855262 T CT +/-
SOD2 A16V rs4880 G GG +/+

SOD2 gene is a member of the iron/manganese superoxide dismutase family. This protein transforms toxic superoxide, a byproduct of the mitochondrial electron transport chain, into hydrogen peroxide and diatomic oxygen. In simpler terms, the more energy your mitochondria produce, the more byproducts (also called free radicals) get produced. These toxic byproducts tear up cell membranes and walls through a process called oxidative stress.  Mutations in the SOD2 gene diminish your ability to transform these toxic byproducts into harmless components.

People with SOD2 polymorphisms may not tolerate nitrates or fish oil well. Mutations in this gene have been associated with idiopathic cardiomyopathy (IDC), sporadic motor neuron disease, and cancer.

PON1 Q192R rs662 C CT +/-
***
TONGUE TIE / CLEFT PALATE
Gene & Variation rsID # Risk Allele Your Alleles & Results
CTH S4031I rs1021737 T GT +/-
IRF6 rs987525 A AC +/-
IRF6 rs861020 A AG +/-
RARA rs7217852 G AA -/-
RARA rs9904270 T CC -/-
TBX22 rs41307258 A T -
TBX22 rs28935177 T A -
***
ALLERGY/MOLD
Gene & Variation rsID # Risk Allele Your Alleles & Results
HLA rs7775228 C TT -/-
HLA rs2155219 T GT +/-
***
IgE
Gene & Variation rsID # Risk Allele Your Alleles & Results
FCER1A rs2427837 A AG +/-
IL-13 C1112T rs1800925 T CC -/-
DARC rs2814778 C TT -/-
IL13 rs1295685 A GG -/-
CD14 rs2569191 C CC +/+
SOCS-1 -820G>T rs33977706 A CC -/-
C3 rs366510 G GT +/-
FCER1A / OR10J2P rs2494262 A AA +/+
FCER1A rs2251746 C CT +/-
RAD50 rs2040704 G AA -/-
RAD50 rs2240032 T CC -/-
***
IgG
Gene & Variation rsID # Risk Allele Your Alleles & Results
FCGR2A rs1801274 A AA +/+
GSTM3 V224I rs7483 T CC -/-
TNFRSF13B rs4792800 G AA -/-
***
IgA
Gene & Variation rsID # Risk Allele Your Alleles & Results
TRAF1 rs3761847 G AG +/-
IRF5 rs4728142 A AA +/+
IGF1R rs2229765 A AA +/+
IFIH1 (HLA) rs1990760 C TT -/-
HLA rs9271366 G AA -/-
CFH rs6677604 A AG +/-
HLA-DQA2 rs9275224 A AG +/-
MTC03P1 rs9275596 C CT +/-
PSMB8 / TAP1 / TAP2 rs9357155 A GG -/-
HLA-DPB2 / COL11A2P rs1883414 A AA +/+
***
CLOTTING FACTORS
Gene & Variation rsID # Risk Allele Your Alleles & Results
CETP rs1800775 C AA -/-
CYP4V2 rs13146272 C AC +/-
GP6 rs1613662 G AA -/-
ITGB3 T196C rs5918 C CT +/-
KNG I598T rs2731672 T CT +/-
NR1I2 rs1523127 C AC +/-
SERPINC1 rs2227589 T CT +/-
HRG rs9898 T CC -/-
F12 rs1801020 A AG +/-
F11 rs2289252 T CT +/-
F11 rs2036914 T CT +/-
F10 113777509 rs3211719 G AG +/-
F7 A353G rs6046 A GG -/-
F2 (Prothrombin 20210A) i3002432 A GG -/-
F3 94997288 rs1324214 A AA +/+
F5 (Factor V Leiden) rs6025 T CC -/-
F9 G580A rs6048 G G +
***
METHYLATION
Gene & Variation rsID # Risk Allele Your Alleles & Results
ACE Del16 rs4343 G AG +/-

ACE (heterozygous mutation) – converts Angiotensin I, a weak vasoconstrictor, into Angiotensin II, a powerful vasoconstrictor, which can cause endothelial dysfunction, free radical stress, and stimulate the release of aldosterone from the adrenal gland. Cofactors are zinc and chloride.

High aldosterone wastes magnesium and potassium, retains sodium, and stiffens the heart. Decreased potassium can lead to fatigue and decreased energy production as cellular membrane activation especially in the brain and peripheral nervous system is dependent upon sodium/potassium balance.

In adults drug therapy and possibly flavonoidshibiscus extract, arginine and pomegranate can be used to block ACE and aldosterone.  In kids, pay attention to electrolyte levels.

ADD1 G460W rs4961 T GG -/-
ACAT1-02 rs3741049 A GG -/-
AGT M235T/C4072T rs699 G AA -/-
AHCY-01 rs819147 C CT +/-
AHCY-02 rs819134 G AG +/-
AHCY-19 rs819171 C CT +/-

AHCY (various heterozygous mutations) – SAMe is the key methyl donor generated from methionine; it is metabolised to homocysteine by AHCY. A defect could create something of a bottleneck, lowering sulphate and ammonia levels. This is not necessarily a bad thing if you have mutations along the transulfuration pathway (i.e. the CBS enzyme), which would cause taurine levels to rise (with a corresponding decrease in glutathione).

I don’t have this problem. Ordinary methylation support is fine in my situation, since this will keep the cycle spinning.

BHMT rs16876512 T CT +/-
BHMT rs6875201 G AG +/-
BHMT-02 rs567754 T CC -/-
BHMT-04 rs617219 C AA -/-
BHMT-08 rs651852 T CT +/-
BHMT R239Q rs3733890 A AG +/-

BHMT (various heterozygous mutations) – enzyme is responsible for converting homocysteine to methionine. It does this by way of a “short cut”, bypassing the normal B12/methylfolate-dependent route.

Mine is probably working less optimally, which isn’t a problem if I improve the status of my methylation cycle via the “long route”. However, taking TMG (Betaine) may get this route functioning optimally.

CBS A13637G rs2851391 T CC -/-
CBS A360A rs1801181 A GG -/-
CBS C19150T rs4920037 A GG -/-
CBS C699T rs234706 A GG -/-
CBS N212N rs2298758 A GG -/-
COMT rs6269 G GG +/+
COMT -61 P199P rs769224 A GG -/-
COMT H62H rs4633 T CC -/-
COMT V158M rs4680 A GG -/-

COMT (one homozygous mutation) – This gene helps break down dopamine and norepinephrine. A defect will cause higher dopamine due to slower breakdown and is associated with ADD/ADHD. Defects will make you more susceptible to dopamine fluctuations, therefore mood swings. People without COMT mutations are generally more even tempered.

My defect isn’t on the V158M gene, which is the key enzyme for breaking down dopamine. Those with mutations on this gene have to be careful with taking too many methyl donors.

COMT must be read along with VDR Taq  — note that my +/+ means I don’t make much dopamine. Taking too many methyl groups when you already have lots floating around (because your mutated gene isn’t using them) can cause mood swings, aggression, etc. This is one reason why some people struggle with mb12. I don’t have this problem because my COMT mutation is balanced by my VDR mutation.

DAO rs2070586 A GG -/-
DAO rs2111902 G GT +/-
DAO rs3741775 C AC +/-
DHFR rs1643649 C TT -/-
FOLR1 rs2071010 A GG -/-
FOLR2 rs651933 A AG +/-
FOLR3 rs7925545 G AA -/-
FOLR3 rs7926875 A CC -/-
FOLR – Folate Receptor genes bind to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate to the interior of cells.
FUT2 rs492602 G GG +/+
FUT2 rs601338 A AA +/+
FUT2 rs602662 A AA +/+

FUT2 gene encodes the fucosyltransferase 2 enzyme which determines “secretor status”. Non-functional enzyme resulting from a nonsense mutation in the FUT2 gene leads to the non-secretor phenotype. It has been shown that non-secretor individuals show significantly reduced bifidobacterial diversity, richness, and abundance. This is significant because intestinal microbiota plays an important role in human health.

FUT2 has been called a robust genetic predictor of vitamin B12 levels by Harvard researchers but so many genes are involved in B12 status I can’t make heads or tails of it yet.

G6PD rs1050828 T C -
G6PD rs1050829 C T -
GAD1 rs3749034 A AA +/+
GAD1 rs2241165 C CC +/+
GAD1 rs769407 C CG +/-
GAD1 rs2058725 C TT -/-
GAD1 rs3791851 C CT +/-
GAD1 rs3791850 A GG -/-
GAD1 rs12185692 A CC -/-
GAD1 rs3791878 T GG -/-
GAD1 rs10432420 A AA +/+
GAD1 rs3828275 T CT +/-
GAD1 rs701492 T CT +/-
GAD1 rs769395 G AG +/-
GAD2 rs1805398 T GG -/-

GAD – these genes encode for glutamic acid decarboxylase which catalyzes the production of GABA.

Glutamate is the main excitatory neurotransmitter in the body and is essential for learning and short and long-term memory.  Glutamate is also the precursor to our primary calming neurotransmitter, GABA.  GABA damps the propagation of sounds so that a distinction can be made between the onset of sound and a background noise.  

Genomic defects, viral illness, and heavy metals will compromise this balance, leading to excess glutamate, insufficient GABA, excitotoxicity, and eventual neuron loss. Aluminum and lead also poisons this enzyme.  

Low GABA leads to impaired speech, anxiety, aggressive behavior, poor socialization, poor eye contact, nystagmus, and constipation.  Glutamate excess does the same and also wastes glutathione and increases levels of TNF-alpha, an inflammatory mediator that can produce gut inflammation.

We can restore glutamate – GABA balance by:

  1. Addressing any CBS up regulation issues to decrease alpha-ketoglutarate production.
  2. Decreasing intake of food precursors of glutamate (includes whey protein, gelatin, soy, peas, tomatoes, parmesan cheese).
  3. Supplementing with GABA
  4. Copper inhibits conversion of glutamate to GABA by glutamate decarboxylase so avoid copper excess, or better stated, an imbalance between copper and zinc.
  5. Calcium is involved in glutamate toxicity, so supplement with magnesium to keep calcium in check.
  6. Remove heavy metals with a chelating agent (toxicity due to mercury is aggravated by glutamate excess – they synergize to damage nerve cells).
  7. Supplementing with Pycnogenol and grape seed extract.
GAMT rs17851582 A GG -/-
GAMT rs55776826 T CC -/-
GIF (TCN3) rs558660 A GG -/-
MAO A R297R rs6323 T T +

MAO A (heterozygous mutation) – Monoamine oxidase A degrades serotonin, dopamine, epineprine, and norepinephrine. This can result in swings in serotonin levels, and therefore mood swings.

If you’re affected, you might want to reduce foods containing high levels of tryptophan. However, it is likely that, as methylation status improves, serotonin fluctuations should also improve (based on improved levels of BH4).

MAT1A rs72558181 T CC -/-
MTHFD1 C105T rs1076991 C CT +/-
MTHFD1 G1958A rs2236225 A AA +/+
MTHFD1L rs11754661 A GG -/-
MTHFD1L rs17349743 C TT -/-
MTHFD1L rs6922269 A GG -/-
MTHFD1L rs803422 A GG -/-
MTHFD – This gene encodes a protein that possesses three distinct enzymatic activities related to folate.

Recent data shows choline requirements are increased by polymorphisms in the phosphatidylethanolamine N-methyltransferase (PEMT) gene (i.e., 5465G->A; rs7946 and -744G->C; rs12325817) and in the methylenetetrahydrofolate dehydrogenase (MTHFD1) gene (i.e., 1958G->A; rs2236225).

Choline is a required nutrient with roles in liver and brain function, lipid metabolism, and fetal development.

MTHFR 03 P39P rs2066470 A GG -/-
MTHFR A1298C rs1801131 G TT -/-
MTHFR A1572G rs17367504 G AA -/-
MTHFR C677T rs1801133 A AG +/-
MTHFR G1793A (R594Q) rs2274976 T CC -/-
MTHFR rs12121543 A CC -/-
MTHFR rs13306560 T CC -/-
MTHFR rs13306561 G AA -/-
MTHFR rs1476413 T CC -/-
MTHFR rs17037390 A GG -/-
MTHFR rs17037396 T CC -/-
MTHFR rs3737964 T CC -/-
MTHFR rs4846048 G AA -/-
MTHFR rs4846049 T GG -/-
MTHFR (heterozygous mutation) – This enzyme has global effects for immune function, muscle metabolism, neurochemical production and regulation, and detoxification.

It is the enzyme most in vogue at the most for analyzing because it’s responsible for converting inactive folate to active folate (i.e. methylfolate) and the +/- defect is common.

rs1801133 – since your +/- is less efficient (operating at 65% of normal), your methylfolate levels may be on the low side. It also suggests that you should stay away from folic acid and, perhaps, too much dietary folate.

MTHFS rs6495446 C CC +/+

MTHFS (homozygous mutation) –  MTHFS is the only enzyme known to catalyze a reaction with folinic acid. If you have a deficiency in this enzyme, and you consume folinic acid (found in vegetables), it will build up in your cells (this is from a note Rich wrote to Fred found here).

The problem with this is that folinic acid normally acts as a regulator of folate metabolism by inhibiting enzymes in this metabolism. In particular, it inhibits the serine hydroxymethyltransferase (SHMT) enzyme, which normally is the main enzyme that converts tetrahydrofolate to 5,10 methylene tetrahydrofolate, which in turn is the substrate for making methylfolate.

So, a deficiency in MTHFS will allow folinic acid to rise inhibiting SHMT, which will lower 5,10 methylene tetrahydrofolate, and thus will also lower production of methylfolate, which is needed by methionine synthase in the methylation cycle.

This would suggest that I need very high levels of methyl folate (and magnesium which is a cofactor). 

MTR A2756G rs1805087 G AA -/-
MTRR A66G rs1801394 G AG +/-
MTRR H595Y rs10380 T CC -/-
MTRR K350A rs162036 G AA -/-
MTRR R415T rs2287780 T CC -/-
MTRR-11 A664A rs1802059 A AG +/-
MTRR rs10520873 C CT +/-
MTRR rs1532268 T CT +/-
MTRR rs162049 G AA -/-
MTRR rs3776467 G AA -/-
MTRR rs9332 A GG -/-

MTRR (homozygous mutation) – Generates the Methyl-B12 used by MTR to convert 5-Methyl-THF into Methionine. With mutation, Methyl-B12 generation is limited, diminishing MTR’s ability to produce Methionine.  Homocysteine toxicity will occur along with impaired formation of S-Adenosyl Methionine (SAMe) and methylation in general.

Suggests inactive B12 supplements wouldn’t work well for me. Supplement also with TMG (trimethylglycine), phosphatidylserine, or phosphatidylcholine.  Avoid dimethylglycine (DMG) which would actually slow down the Homocysteine to Methionine conversion.

NOS1 rs3782206 T CC -/-
NOS2 rs2297518 A GG -/-
NOS2 rs2274894 T TT +/+
NOS2 rs2248814 A AA +/+
NOS3 rs1800783 A TT -/-
NOS3 rs1800779 G AA -/-
NOS3 rs3918188 A AA +/+
NOS3 G10T rs7830 T GG -/-
NOS3 T786C rs2070744 C TT -/-

NOS (some homozygous mutations) – in a process dependent on BH4, NOS converts arginine into nitric oxide and assists in ammonia detoxification. In the absence of BH4, NOS will convert Arginine into peroxynitrite or superoxide, which are both bad free radicals.

I may benefit from reducing protein intake, eating Yucca or butter with meals, or supplementing with butyrate or BH4 to keep ammonia levels down. Thankfully, I don’t have a CBS upregulation, which would have an additive effect.

PEMT rs4244593 T GT +/-
PEMT rs4646406 A AT +/-
PEMT rs7946 C TT -/-

PEMT – This gene encodes an enzyme which converts phosphatidylethanolamine to phosphatidylcholine (the most abundant mammalian phospholipid) by sequential methylation in the liver.

Mutations may mean I’d benefit from supplementing choline or eating more eggs.

SHMT1 C1420T rs1979277 A AG +/-
SHMT1 rs9909104 C TT -/-
SHMT2 rs12319666 T GG -/-
SHMT2 rs34095989 A AG +/-
SHMT – Serine hydroxymethyltransferase (SHMT) is an enzyme which plays an important role in cellular one-carbon pathways by catalyzing the reversible, simultaneous conversions of L-serine to glycine (retro-aldol cleavage) and tetrahydrofolate to 5,10-methylenetetrahydrofolate (hydrolysis). This reaction provides the largest part of the one-carbon units available to the cell.

SHMT is a member of the PLP or P5P (B6) enzyme class. P5P is needed by both mSHMT and cSHMT at all times to activate this enzyme.

Dr. Yasko puts SHMT first of the first priority mutations because it is a dead end pathway. If it’s blocked, it takes your folate and holds it there so you won’t get it converted into folinic or 5MTF. This means it steals this from the rest of the cycle. She also notes, “People with the SHMT and/or ACAT mutations sometimes have a greater tendency to experience gut dysbiosis and imbalanced flora.”

SLC19A1 rs1888530 T CT +/-
SLC19A1 rs3788200 A AG +/-

SLC19A1 – The membrane protein encoded by this gene is a transporter of folate and is involved in the regulation of intracellular concentrations of folate.

TCN1 rs526934 G AA -/-
TCN2 C766G rs1801198 G CG +/-
TCN – the “frailty” genes. TCN1 and 2 are both B12-binding and transport proteins but TCN2 is the primary of the two. Both deliver cobalamin to cells.
TYMS rs502396 C CC +/+
TYMS – A nasty cancer gene (the mutation). Thymidylate synthase catalyzes the methylation of deoxyuridylate to deoxythymidylate using 5,10-methylenetetrahydrofolate (methylene-THF) as a cofactor. This function maintains the dTMP (thymidine-5-prime monophosphate) pool critical for DNA replication and repair.
VDR Bsm rs1544410 T TT +/+

VDR – Bsm/Taq mediates an increase in dopamine production in response to Vitamin D (VDR is an abbreviation for Vitamin D Receptor). The (+/+) form is less active, so you tend to be low in dopamine.  Methyl status will be low also, so you will be less sensitive to supplementation with methyl groups. 

I have (+/+), which read with my normal V158M gene means that I have low vitamin D levels, poor tolerance to toxins and microbes, make less dopamine and need and tolerate more methyl donors.

***
CELIAC DISEASE/GLUTEN INTOLERANCE
Gene & Variation rsID # Risk Allele Your Alleles & Results
HLA rs2858331 G AG +/-
HLA DQA1 rs2187668 T CC -/-
***
THYROID
Gene & Variation rsID # Risk Allele Your Alleles & Results
CTLA4 rs231775 G AA -/-
FOXE1 rs1867277 A GG -/-
FOXE1 rs7043516 C AA -/-
FOXE1 rs10984009 A GG -/-
***
EYE HEALTH
Gene & Variation rsID # Risk Allele Your Alleles & Results
BCMO1 rs4889294 C CT +/-
BCMO1 R267S rs12934922 T AT +/-
BCMO1 A379V rs7501331 T CC -/-
***
MITOCHONDRIAL FUNCTION
Gene & Variation rsID # Risk Allele Your Alleles & Results
ATP5g3 rs185584 G AA -/-
ATP5g3 rs36089250 C TT -/-
ATP5c1 rs2778475 A AG +/-
ATP5c1 rs1244414 T CC -/-
ATP5c1 rs1244422 T CT +/-
ATP5c1 rs12770829 T CT +/-
ATP5c1 rs4655 C CT +/-
COX5A rs8042694 G AG +/-
COX6C rs4626565 C TT -/-
COX6C rs7844439 A CC -/-
COX6C rs4510829 A GG -/-
COX6C rs1135382 A GG -/-
COX6C rs7828241 C AA -/-
COX6C rs12544943 G AA -/-
COX6C rs4518636 C TT -/-
NDUFS3 rs2233354 C TT -/-
NDUFS3 rs4147730 A AG +/-
NDUFS3 rs4147731 A GG -/-
NDUFS7 rs2332496 A AA +/+
NDUFS7 rs7254913 G AA -/-
NDUFS7 rs1142530 T TT +/+
NDUFS7 rs7258846 T TT +/+
NDUFS7 rs11666067 A AA +/+
NDUFS7 rs2074895 A AA +/+
NDUFS7 rs809359 G AA -/-
NDUFS8 rs4147776 C AA -/-
NDUFS8 rs1122731 A GG -/-
NDUFS8 rs999571 A GG -/-
NDUFS8 rs2075626 C TT -/-
NDUFS8 rs3115546 G TT -/-
NDUFS8 rs1104739 C AC +/-
NDUFS8 rs1051806 T CC -/-
UQCRC2 rs6497563 C CT +/-
UQCRC2 rs4850 A GG -/-
UQCRC2 rs11648723 T GG -/-
UQCRC2 rs12922362 A AC +/-
UQCRC2 rs2965803 T CC -/-
***
OTHER IMMUNE FACTORS
Gene & Variation rsID # Risk Allele Your Alleles & Results
4q27 Region rs6822844 T GG -/-
APOE rs429358 C TT -/-
ATG16L1 rs10210302 C CT +/-
GSDMB rs7216389 T CT +/-
HLA-DRB1 rs660895 G AA -/-
IL5 rs2069812 A AG +/-
IL-13 rs20541 A GG -/-
IL4R Q576R rs1801275 G AA -/-
MeFV A744S i4000409 A CC -/-
MeFV E148Q rs3743930 G CC -/-
MeFV F479L i4000403 C GG -/-
MeFV K695R i4000407 C TT -/-
MeFV M680I rs28940580 G CC -/-
MeFV M694I rs28940578 T CC -/-
MeFV M694V i4000406 C TT -/-
MeFV P369S rs11466023 A GG -/-
MeFV R761H i4000410 T CC -/-
STAT4 rs10181656 G CG +/-
TNF -308 rs1800629 A GG -/-
TNF -238 rs361525 A AG +/-
TYR (MeFV) V726A rs28940879 A GG -/-
***
SULFONOTRANSFERASE
Gene & Variation rsID # Risk Allele Your Alleles & Results
SULT1A1 rs35728980 G TT -/-
SULT1A1 rs1801030 C TT -/-
SULT1A1 rs1042157 A NO CALL &nbsp
SULT1A1 rs36043491 T CC -/-
SULT1A1 rs60749306 C TT -/-
SULT1A1 rs9282862 C TT -/-
SULT1A1 rs1042008 A GG -/-
SULT1A1 rs2925627 C TT -/-
SULT1A1 rs2925631 C TT -/-
SULT1A1 rs3020800 G AA -/-
SULT1A1 rs4149385 T CC -/-
SULT1A1 rs60701883 A CC -/-
SULT1A1 rs4149381 G TT -/-
SULT1A1 rs8057055 A CC -/-
SULT1A1 rs6498090 A GG -/-
SULT1A1 rs7193599 C AA -/-
SULT1A1 rs7192559 T CC -/-
SULT1A3 rs1059667 A TT -/-
SULT2A1 rs296366 T CC -/-
SULT2A1 rs296365 C GG -/-
SULT2A1 rs11569679 T CC -/-
SULT2A1 rs4149452 T CC -/-
SULT2A1 rs8113396 G AA -/-
SULT2A1 rs2547242 C TT -/-
SULT2A1 rs2910393 T CC -/-
SULT2A1 rs4149449 T CC -/-
SULT2A1 rs2547231 C AA -/-
SULT2A1 rs4149448 G AA -/-
SULT2A1 rs11083907 A GG -/-


Some background information from Genetic Genie:

We have two copies of most of the genes we are born with – one from our mother and one from our father. Genetic Genie uses the SNPs (Single Nucleotide Polymorphisms) generated from your unique DNA sequence to determine if one or both copies of your genes have a mutation at a specific location in a specific gene. If there are no mutations present, your result will be displayed as (-/-). If one gene is mutated, the result will read (+/-). If both copies have a mutation, the result is (+/+). Along with the (+/-) symbols, the colors on the table also denote the type of mutation for visual comprehension. The color red indicates a homozygous (+/+) mutation, the color yellow indicates a (+/-) heterozygous mutation and the color green (-/-) indicates that you don’t carry the specific mutation.

The terms heterozygous and homozygous are used by geneticists to denote whether one or both copies of a gene are mutated. Heterozygous mutations (+/-) may differ from homozygous mutations (+/+) in associated disease risk since a person with a heterozygous mutation will often still have one fully functioning copy of the gene. It is also important to understand that having a gene with a SNP mutation does not mean that the gene is defective or nonfunctioning, only that it is working with an altered efficiency. Sometimes this means that it is working at a decreased level, but it could also mean that it is functioning at a higher than normal efficiency, or that the gene is lacking regulatory mechanisms normally involved in its expression.

Although mutations can occur at any time during our lifetime, it is most likely that we are born with these mutations and will have them throughout our life. These inherited mutations have been passed down to us from previous generations (our parents and grandparents) and may be passed to future generations (our children). This may provide an explanation as to why certain traits or diseases “run in the family”.

Although we cannot change our genetic code, we can change how our genes are expressed. Research has revealed that our gene expression is not determined solely by hereditary factors, but it is also influenced by our diet, nutritional status, toxic load and environmental influences or stressors.

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22 comments…

  • avatar

    madrona February 17, 2014, 6:35 am

    Did you get all of the above genetic info via Genetic Genie?? I just ran my 23andme data and didn’t get nearly what you got. I wonder if it’s because 23andme cut down on the number of snps they are looking at. 

    Reply
    • avatar

      Eric February 17, 2014, 3:19 pm

      It came from Sterling’s App…

      Reply
      • avatar

        Marie April 6, 2014, 3:54 pm

        Hi Eric,
        This post was really great, I didn’t know a lot of these SNPs until I came across your site! Did the explanations for the SNPs come with Sterlings App? From your site, I learned I have mutations in MTHFS and MTHD but there is not a lot of information that I can find on the “lesser known” SNPs. 

        Reply
        • avatar

          Eric April 7, 2014, 7:36 pm

          I don’t think those explanations came with sterling’s app – they were pieced together from all over the place… Glad you found it helpful!

          Reply
  • avatar

    Linda February 6, 2014, 9:48 pm

    Been at this awhile (2004). Got kicked out of Yasko’s forum on second post back in 2005 or 2006. So- have been out in http://www.genecards.org, OMIM, pubmed, etc. ever since with good results.

    Yes in fact, our small group has collectively verified that there is a lovely real life model of impaired methylation and it’s role in chronic disease. Optimize methylation and hurray- return to health in so many ways.  In our experience, yes, it is TRICKY!—and must be individualized–and sometimes using food is less problematic than supplements.. But details on all that to follow (hopefully sometime in the next few years!)

    My question:  I’m going crazy.  I wanted to verify a few assumptions in the Genetic Genie reports (God Bless her!) In doing so, I see that so many genetic variations presented as “mutations” by Dr Yasko can also be very common genetic “differences” for lack of a better word. For example MAO A.   see http://www.snpedia.com/index.php/Rs6323   The distribution in various populations is in the graph at the bottom right corner.    I was a bit surprised  to see that in many ethnic groups, Yasko’s “MAO A (+,+)” is the predominant allele. and well past 80% in a few of the populations. 

    That was a bit of an eye opener for me.   On average, more than 1/2 of the population is walking around with this ‘mutation.’  Most Yasko followers will assume mutation = problem.  I wonder- is that valid?  I can completely buy that variations in MTHFR, MTRR etc matter more now than they did in previous generations (back then we ate real, nutritious , seasonal, vegetables and didn’t fortify our foods with fake folic acid etc)  

    However, after poking around in a few different places,  I just want to verify that what we have all been taught are “mutations” are actually significant enough to need intervention!

    Top on my list today is SOD2 A16V rs4880. I’m confused:  Genetic Genie lists  GG as  +,+ mutations.  Clicking through http://www.genecards.org I can verify A,G are alleles. however most articles and http://www.snpedia.com/index.php/Rs4880  talk about CC, CT, TT and their impact on various disease states- with the highest risk listed as C,C. (ClinVar bottom right of page)  

    My question:  is it safe to assume G,G listed as a +,+ mutation is synonymous with C,C discussed as a risk factor in various articles?  Does any of this matter??  I guess my point, is that- in real life, yes optimizing methylation matters to overall health, but I don’t want to blindly assume everything out there matches real life.  I like multiple sources.  Thank you- any and all- who can help answer my questions.

    Blessings, Linda
    PS If you haven’t seen this- http://www.ctdbase.org have a look. Type in any gene and you’ll have a field day with verified disease associations and chemical interactions (ways to “speed up” or “slow down” various functions)
     
     
     

    Reply
    • avatar

      Eric February 6, 2014, 10:04 pm

      You make an excellent point Linda and my interpretation is that these genetic ‘differences’ only matter if they happen in a certain combination and you happen to be exposed to something that your genetic vulnerabilities can’t handle. I think that’s what happened to us. As for your specific questions, sorry they are still over my head. Maybe after another year of chelation and methylation protocol I’ll be sharper, lol. Be well!

      Reply
  • avatar

    Brad November 24, 2013, 12:35 pm

    Hi,
    Great job on the site. I just wanted to comment that IMO it would be more accurate to say that rs1135840 is involved in the metabolism of approximately 25% of all medications including most psych meds including antipsychotics and antidepressants.
    brad

    Reply
    • avatar

      Eric November 24, 2013, 4:39 pm

      Thanks Brad! I just updated it:)

      Reply
      • avatar

        Luna February 26, 2014, 2:54 am

        Okay, this is the one I that brought me to this site. Does someone with a homozygous variation there OVERmetabolize or UNDERmetabolize these drugs? 
        Yes, TOTAL newbie here. :)

        Reply
  • avatar

    Eric November 19, 2013, 10:28 pm

    I’ve learned a lot since first posting about my genetics and have been adding the research underneath the related results above. 23andme just finished my ancestry results and amazingly they show my mother’s maiden name as the top relative surname based on my DNA!

    Reply
  • avatar

    Mary November 15, 2013, 11:46 am

    Really rooting for you to reach optimal health Eric!  

    Reply
    • avatar

      Eric November 15, 2013, 5:43 pm

      thanks Mary :D

      Reply
  • avatar

    Leon November 14, 2013, 1:02 pm

    Like you, they were actually pretty good! I’d go as far as to say that, were I to have been born 50 years earlier, I would be a bastion of good health. The toxic environment we now live in has put strain on those with methylation dysfunction, when it would have likely caused little trouble some years ago.
     

    NAME CONFIDENCEYOUR RISKAVG. RISKCOMPARED TO AVERAGE

    Age-related Macular Degeneration

    8.4%
    6.5%
    1.29x

     

     

    Colorectal Cancer

    6.9%
    5.6%
    1.24x

     

     

    Type 1 Diabetes

    5.3%
    1.0%
    5.23x

     

     

    Chronic Kidney Disease

    4.2%
    3.4%
    1.22x

     

     

    Restless Legs Syndrome

    2.5%
    2.0%
    1.25x

     

     

    Celiac Disease

    0.48%
    0.12%
    4.08x

     

     

    Reply
    • avatar

      Eric November 14, 2013, 10:32 pm

      Congratulations Leon, we all need a little bit of luck now and then!

      Reply
  • avatar

    Leon November 13, 2013, 5:07 pm

    The results are quite interesting; they mainly suggest I need to be careful with methyl donors (COMT +/+ and VDR Taq +/-). I am slow at regenerating methyl b12 from methyl groups and b12 (MTRR), which, combined with my intolerance for methyl groups, is going to make treatment tricky. Whilst I would want to overcome this with active b12, I have to respect that I can easily OD on methyl groups. This is problematic given that inactive b12 is probably going to sit around doing nothing if I take it. So, I suspect I will try a little of both, and add some adb12 in there.
    The complete genetic genie results were:

    Gene & Variation

    rsID

    Alleles

    Result

    COMT V158M

    rs4680

    AA

    +/+

    COMT H62H

    rs4633

    TT

    +/+

    COMT P199P

    rs769224

    GG

    -/-

    VDR Bsm

    rs1544410

    CT

    +/-

    VDR Taq

    rs731236

    AG

    +/-

    MAO A R297R

    rs6323

    G

    -/-

    ACAT1-02

    rs3741049

    AG

    +/-

    MTHFR C677T

    rs1801133

    AG

    +/-

    MTHFR 03 P39P

    rs2066470

    GG

    -/-

    MTHFR A1298C

    rs1801131

    GT

    +/-

    MTR A2756G

    rs1805087

    AA

    -/-

    MTRR A66G

    rs1801394

    GG

    +/+

    MTRR H595Y

    rs10380

    CC

    -/-

    MTRR K350A

    rs162036

    AA

    -/-

    MTRR R415T

    rs2287780

    CC

    -/-

    MTRR A664A

    rs1802059

    AG

    +/-

    BHMT-02

    rs567754

    CT

    +/-

    BHMT-04

    rs617219

    AC

    +/-

    BHMT-08

    rs651852

    CT

    +/-

    AHCY-01

    rs819147

    CT

    +/-

    AHCY-02

    rs819134

    AG

    +/-

    AHCY-19

    rs819171

    CT

    +/-

    CBS C699T

    rs234706

    AG

    +/-

    CBS A360A

    rs1801181

    GG

    -/-

    CBS N212N

    rs2298758

    GG

    -/-

    SHMT1 C1420T

    rs1979277

    AG

    +/-

     
     
     

    Reply
    • avatar

      Eric November 13, 2013, 5:13 pm

      Sorry to hear about your Catch-22! Even without that problem, I have found increasing methylation a rocky process… what about the other standard 23andme reports? how did you fare with those?

      I’ll be filling and more info on this page over the next month or so, some interesting things from Brad and areas to research, but it will take time.

      Reply
  • avatar

    Leon November 13, 2013, 1:29 pm

    Incidentally, I’ve just this morning received my own results. I used geneticgenie, org. This is free, though they do ask for a donation, if possible. I notice that they provide you with the key SNPs, which means it isn’t as comprehensive as the one you’ve received. However, with your results they do provide an overview of what each SNP means, taken from the work of Ben Lynch and Amy Yasko. This section also provides treatment tips. I think this would be a good primer, if you’re interested.
     

    Reply
    • avatar

      Eric November 13, 2013, 4:08 pm

      Thanks Leon, I just happened to run my data through genetic genie yesterday and included some of the explanation text on this page below the report. Notice that I incorporated your notes into the report section. Going to do that with more info that I have that came from Brad too… how do your results look?

      Reply
  • avatar

    Expat Viking November 12, 2013, 8:57 pm

    WOW indeed!
    This whole activity really feels like russian dolls: once you think that you have somewhat figured things out, another doll opens up and you realise that you know nothing….
    Anyway, very, very interesting info from Leon but it feels like it would take at least a month to get a handle on it.
    It will be very interesting to follow you Eric when you apply your considerable systematic energy to this.

    Reply
    • avatar

      Eric November 12, 2013, 9:15 pm

      Yep, Russian dolls and onion peeling for sure! I’m pretty surprised at how inaccessible the genetic info is right now… The tools I’ve seen so far seem pretty crude and online information geared towards scientific types. Pretty amazing, though, what $99 can get you today!

      Reply
  • avatar

    Leon November 12, 2013, 2:50 pm

    AHCY (various heterozygous mutations) – SAMe is the key methyl donor generated from methionine; it is metabolised to homocysteine by AHCY. A defect could create something of a bottleneck, lowering sulphate and ammonia levels. This is not necessarily a bad thing if you have mutations along the transulfuration pathway (i.e. the CBS enzyme), which would cause taurine levels to rise (with a corresponding decrease in glutathione). You don’t have this problem. Ordinary methylation support is fine for this, since this will keep the cycle spinning.
    BHMT (various heterozygous mutations) – enzyme is responsible to converting homocysteine to methionine. It does this by way of “short cut”, missing out the normal B12/methylfolate-dependent route. Yours is probably working less optimally, which isn’t a problem if you improving the status of your methylation cycle via the “long route”. However, you could consider taking TMG (Betaine) to get this route moving optimally.
    COMT (one homozygous mutation) – this isn’t the V158M gene, which is the key enzyme for breaking down dopamine. Those with mutations on this gene have to be careful with taking too many methyl donors, because the gene uses methyl donors to break down dopamine. However, it must be read along with VDR Taq (note that +/+ means you don’t make much dopamine), which is responsible for generating dopamine. Taking too many methyl groups when you already have lots floating around (i.e. because your mutated gene isn’t using them) can cause mood swings, aggression, etc. This is why I think some people struggle with mb12.
    VDR – Yours is (+/+), which read with your normal V158M gene means that you have lower vitamin D levels, have poor tolerance to toxins and microbes, make less dopamine and need and tolerate more methyl donors. (Hence why you can probably tolerate high doses of methyl donors.)
    MAO A (heterozygous mutation) – responsible for breaking down serotonin. This can result in swings in serotonin levels, and therefore mood swings. If you’re affected, you might want to reduce foods containing high levels of tryptophan. However, it is likely that, as methylation status improves, serotonin fluctuations should also improve (based on improved levels of BH4).
    MTHFR (heterozygous mutation) – present in a high level of the population. It is the enzyme most in vogue at the most for analysing. It is responsible for converting inactive folate to active folate (i.e. methylfolate). Since yours is less efficient, your methylfolate levels may be on the low side. It also suggests that you should stay away from folic acid and, perhaps, too much dietary folate.
    MTHFS (homozygous mutation) – very interesting! Would suggest that you need very high levels of methyl folate. To explain this, Rich wrote Freddd a really interesting note, which I’ve reproduced below (http://forums.phoenixrising.me/index.php?threads/attention-freddd-mthfs-deficiency.11524/):

    Hi, Freddd.

    I’ve been thinking about your body’s intolerance of folinic acid and of vegetable-based folates. Vegetables contain folinic acid as well as methylfolate, and lettuce, spinach, carrots and peppers contain significant amounts of folinic acid. I suspect that it is the intolerance of folinic acid that causes your body to be intolerant of vegetable-based folate, also.

    Here’s what I suspect accounts for this. I suspect that you have an inherited deficiency in the enzyme methenyltetrahydrofolate synthetase (MTHFS). This is the only enzyme known to catalyze a reaction with folinic acid. If you have a deficiency in this enzyme, and you consume folinic acid, it will build up in your cells. The problem with this is that folinic acid normally acts as a regulator of folate metabolism by inhibiting enzymes in this metabolism. In particular, it inhibits the serine hydroxymethyltransferase (SHMT) enzyme, which normally is the main enzyme that converts tetrahydrofolate to 5,10 methylene tetrahydrofolate, which in turn is the substrate for making methylfolate.

    So, a deficiency in MTHFS will allow folinic acid to rise, and this will inhibit SHMT, which will lower 5,10 methylene tetrahydrofolate, and thus will also lower production of methylfolate, which is needed by methionine synthase in the methylation cycle.

    I think this can explain why folinic acid has been so devastating to you and why its effects are so persistent, once you have ingested it. It builds up, because the enzyme that normally controls its level by converting it to 5,10 methylene tetrahydrofolate is deficient. It stays high for a long time for the same reason. When it is high, it suppresses the SHMT reaction, which lowers the natural production of methylfolate, which then inhibits methionine synthase and partially blocks the methylation cycle.

    This would also explain why you have had to take such high dosages of methylfolate, especially if you have taken some folinic acid or vegetable-based folates, which contain folinic acid. The reason is that your normal production of methylfolate has been inhibited, so that you have to supply it exogenously. I suspect that in addition, your tetrahydrofolate is probably high, because it is the product of the methionine synthase reaction, and if SHMT is inhibited, that will tend to inhibit the conversion of THF to 5,10 methylene THF, so that THF would probably rise. High THF will likely exert backpressure (product inhibition) on the methionine synthase reaction, so that it is necessary to add more methylfolate to drive it at a normal rate.

    I think it would be very interesting to see the results of a methylation pathways panel on you. This panel measures a range of folate forms, and I think it would give some unusual results in your case.

    Best regards,

    Rich  

     
    MTRR (homozygous mutation) – MTR combines methylfolate and homocysteine to form methionine and THF. A defect is an upregulating, which would place greater demands on mb12 to provide the necessary b12 needed for the reaction. MTRR is important because it serves the MTR enzyme with mb12. You have several mutations in a variety of these genes, which may mean you are low in mb12. As I say, without this you cannot convert homocysteine to methionine, and therefore methyl donors such as SAMe are not produced optimally. This portion of your test means that inactive b12 wouldn’t work well for you.
     
    NOS (some homozygous mutations) – these enzymes are responsible for detoxifying ammonia. High ammonia is obviously undesirable, so you may benefit from reducing your protein intake, or supplementing according (e.g. yucca with meals) to keep levels down. Thankfully, you don’t have a CBS upregulation, which would have an additive effect on levels.

    Hope that helps. It seems as though you’re already supplementing according to your genetics. I’m sure others will have more…
    Best,
    Leon

    Reply
    • avatar

      Eric November 12, 2013, 4:05 pm

      WOW Leon, this is so helpful, thank you for your effort, you’re very kind!!

      It will take me a long time to work through your information and what I got from my phone conversation with Brad, and I will be trying to figure out what the best way to organize the information might be, so it can help others too.

      -eric

      Reply

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My name is Eric - I‘m 45 and first saw a doctor for fatigue at 17. I lived fairly normally if a little subdued by lack of endurance. But then, 12 years ago I fell into a nosedive after moving to South Florida. Now, I know my problems stem from heavy metal toxicity and methylation cycle dysfunction. I'm in the process of chelating the metals out and starting up methylation. This is where I blog about the process. More about me here.

Timeline and current dosing:

Rounds completed: 22
Total chelation days: 89
Dose: 50 mg DMSA and 37.5 mg ALA every 2 hrs

* supplements
* hair test
* genetics
* lessons learned

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