My genetics

elevated-risk[Y]esterday 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. Here’s a list of analyzers:

My results from Sterling’s app 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 and may be one of the key sources of my troubles. 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.

Now what about SOD1 & 3? I don’t know why it doesn’t appear on this report but I was able to get some information on it from Livewello and it looks like I am much better off there. Here’s my SOD1 and SOD3 status. Just for kicks, I decided to run SOD2 and I find it shows a much different picture than sterling’s app: my SOD 2 on Livewello. Notice how it shows that I do have some working SOD2  genes!

PON1 Q192R rs662 C CT +/-
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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
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ALLERGY/MOLD
Gene & Variation rsID # Risk Allele Your Alleles & Results
HLA rs7775228 C TT -/-
HLA rs2155219 T GT +/-
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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 -/-
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IgG
Gene & Variation rsID # Risk Allele Your Alleles & Results
FCGR2A rs1801274 A AA +/+
GSTM3 V224I rs7483 T CC -/-
TNFRSF13B rs4792800 G AA -/-
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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 +/+
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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 +
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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. Check out what Sterling says: The 3 major FUT2 genes that seem to cause problems are FUT2 A12190G, FUT2 G12447A and FUT2 G12758A. When these three SNPs are homozygous, these people cannot make H antigen. Why is H antigen important? . . . Almost everyone to date who has been diagnosed with ulcerative colitis and Crohn’s disease are homozygous for these three particular mutations. These three FUT2’s play a huge role in autism. . . More or less, if you are lacking the ability to produce H antigen in the gut, your probiotics will not have anything to stick to in the gut. I normally do not recommend products and I am not affiliated with Klaire Labs in any way but they do have a prebiotic called Galactomune that contains galactooligosacchrides and beta-glucan. These are essential for anyone with the above FUT2’s homozygous in order for probiotics to stick to their gut and be utilized.
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. Deficiency leads to liver disease.
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. “Studies have recently shown that because of common genetic polymorphisms, choline deficiency is a widespread problem. Men, postmenopausal women, and premenopausal women with PEMT SNPs need to increase choline intake in the diet to offset elevated risk of liver dysfunction.”
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 SLC19A1 gene encodes a transporter involved in folate and thiamine uptake and may play a role in intracellular folate distribution [21].
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.
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CELIAC DISEASE/GLUTEN INTOLERANCE
Gene & Variation rsID # Risk Allele Your Alleles & Results
HLA rs2858331 G AG +/-
HLA DQA1 rs2187668 T CC -/-
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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 -/-
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EYE HEALTH
Gene & Variation rsID # Risk Allele Your Alleles & Results
BCMO1 rs4889294 C CT +/-
BCMO1 R267S rs12934922 T AT +/-
BCMO1 A379V rs7501331 T CC -/-
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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 -/-
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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.

178 thoughts to “My genetics”

  1. Eric did you made some conclusive decisions after you digested all this genetic information ? I mean did it helped you improve your health ? Where I live it’s expensive to do this test, so I am wondering if it would help. Thanks !

    1. The answer is yes absolutely – I consider the genetic information priceless. That said, I’m still not well yet and have a long way to go. But going in the right direction is still everything!

    2. You can get the testing for $99 on 23andme.com and go to livewello and the other sites Eric lists above to have them analyzed better

  2. Hi Eric, I have so many similar snps to you…..I’d be really interested to know what supplements you use. I have quite a list already and am happy to post those but very interested to know what you use.

  3. This is a great site. Thank you for all of the information. Does Brad freelance? Or does anyone know a consultant in this area? Thanks!

    1. Sorry, I don’t know the answer to that Barbara but a good place to start would be to post on Phoenix Rising asking for help…

  4. This is so informative. I am recovering from fluoroquinolone toxicity syndrome and other issues. Doctors haven’t helped but learning about my gene mutations and snps has helped. I get info here and there but nothing like you have been able to uncover. Where did you get all of this information? Do you recommend certain sites or programs? I have done the following: Livewello, Nutrahacker, MTHFR Support, Genetic Genie, and Prometheus. It is still hard to figure out if I am on the right track.

    1. hi Brooke, this information came from here and there – online research and from talking to someone else on the phone who’d been through this process… Sorry I don’t have any good leads for you! I know how difficult it is…

  5. Dave Asprey of Bulletproof Exec has just finished a documentary called “Moldy”. It should cover just about all current research on mold and mycotoxins.

  6. Something else to rule out: 25% of people are genetically susceptible to mold. They are diagnosed as having chronic fatigue. The mold/bacterial combo in buildings effects mitochondrial activity/energy, it causes crazy aches and pains, fibromyalgia, brain fog, crazy inflammation, effects your adrenals and thyroid, appears related to some autoimmune diseases etc. I think everyone with chronic fatigue should rule out living in a water-damged building (sometimes hard to tell). Additionally, that 25% has trouble removing mycotoxins from their body and even if they lived in a water-damaged building and moved they may still have mycotoxins in their body creating a chronic inflammatory state until they remove them.

    1. Right on, Sharol – I know I have mold allergy and I know I have molds living in my digestive system, I’ve got the pictures.

      I’ve been unable to find any information about mold growing in the body online. It seems incredible to me, but there really isn’t much.

      Search Google for “Can mold grow in your intestines?” and you will end up reading about Candida which I don’t have. There are probably thousands or millions of species of fungi and what’s to stop them from living inside you, creating your own mycotoxin factory? I know what is supposed to stop them – healthy gut bacteria and a healthy SOD2 system, and I must be lacking both.

      1. The problem is mycotoxins. There are also other toxic products that are put out in water damaged buildings, but mycotoxins is a big part of it. People who are genetically susceptible can not get they mycotoxins out of their body. I have been posting things on my website to help folks as I went though this myself in the past. It is kind of complicated as it involves making sure you are out of a water-damaged building first and foremost or treatment won’t work. I lived in two water-damaged homes in my distant past and they haunted me for years until I figured out my issue. Mycotoxins can also cause mitochondrial damage. They often effect endocrine organs such as adrenals, and thyroid. There are so many things that can be effected, it is like a house of cards falling down at its worst. I will give you a web page on my website that has quite a bit of data. I apologize for everything not being up there yet and for it being technical. I have many things in my life that keep me from spending the time needed to sit down and focus only on finishing the site data. Although, I am a practitioner myself, please do not simply follow what is listed there. It really is for education only. Eveyrone is different. I would read what might apply to you and then find a practitioner you can work with who will identify if you do have a mold susceptibility. They should also see if you have other genetic issues that might effect your biochemical network, and can then help you adjust your environment, diet and suggest supplements. There is one item that is a drug that I found invaluable to remove mycotoxins called cholestyramine. I and others I have worked with have tried clay, charcoal, water soluble fibers etc. but none work well compared to choestryramine. We are still looking for other methods but so far choelstyramine has been very helpful. I have 3 pages on cholestyramine on the website to help folks understand it. Again, I apologize for my messy website. I am in the process of looking for some help to make a new website that will be easier for folks to use and easier for me to get data into. Go to http://www.herbaltransitions.com and click on mold biotoxins and biotransformational pathways. That will take you to the page with links that might help a little more. I welcome feedback on how to make the new website better. I will try to get time next week to go in and finish adding things to the treatment/supplement page as I realize this is a page that is helpful to many folks for ideas to take to their Docs.

        1. Fortunately I live in a very clean dry environment and have for the past eight years. We lost just about everything we had when we moved out of Florida to get away from the mold! don’t think I can take a chance on cholestyramine because my cholesterol has been too low for a very long time probably due to mercury toxicity. so for now, I’m relying on charcoal…

  7. HELP! I am so overwhelmed with info and lack of what in the world it all means! I’ve performed the 23 and me, received results, uploaded to Livewello (can’t figure it out at all), then up loaded MTHFRsupport (still ???). My functional meds doc performed genetic testing, I know I’m MTHFR but not clear on what degree. I know I have a risk for heart disease, and Alzheimer’s, and apparently I was destined for the Thyca I had 3 years ago.
    Doc has thrown supplements at me to try and I keep have adverse reactions to them.
    Where do I go from here for information to identify what these SNPS mean and what if anything I can do to combat them. I’m not a scientific grasping person, this is all so overwhelming I just wanna cry.
    Can you please point me to a “dumbed down” version of this info so I can figure out the supplements I need?
    Appreciate all your efforts to help

    1. Sandy, I don’t know of any real basic version of the genetic stuff. It is difficult to say the least. What kind of doctor are you seeing? Which supplements did you have adverse reactions to? Many people have to titrate up methylation supplements from very very low doses…

  8. Wow! There is so much info with what you used – I used Livewello and that was overwhelming enough. I was curious about the VDR- I have the same result there- Is there anything specifically you’ve done for this? Add K2, magnesium? Not sure what else I can do to help and you’ve been at it longer so thought I’d ask:)

    1. hi Ann, I do take a lot of magnesium and also took K2 for a long time. I recently dropped the K2 as I’m trying to cut back on all my supplements and because taking $700 worth of supplements a month did not really do the trick…

  9. Thanks you so much for all the investigating you have been doing to help people decipher all the raw data from “23 and me ” and a like companies . Awesome you really made my day today a lot easier!!!! 🙂 Knowledge is power.
    Thanks Ingrid

      1. Hi Eric, Thanks for making your research available to us. There is a mystery I have been working on for a while and I think your explanations of snp’s above may have given me a few more clues. About a year ago I had a methylation test done by Vitamin Diagnostics. The results were depressing and odd. The depressing part was that I have too much glutathione in the wrong form and not enough in the right but the odd thing was my folinic acid was extremely low. In fact the doctor there wanted to my get to about 30 mg to correct which scared the hell out of me. I think I got to 5 mg and then backed down. But recently I have been feeling odd again like there is a ceiling I can’t break through health wise. I checked some of my supplements I take for tendonitis and neck and shoulder stiffness and they have methy b’s and MSM). I know you can’t answer this question from a metabolic perspective but can you tell me if my logic is sound? My snp’s mirror yours in the range of about 85-90%. The relevant snp’s I think, are:

        MTHFR ++
        MTHFS +-
        COMT ++
        COMT 158 VM++
        SHMT 1 C1420T +-
        SHMT +-
        SHMT2 —
        SHMT2 —
        VDR BSM ++
        BHMT —
        BHMT–
        BHMT 02 ++
        BHMT 04 +-
        BMT 08 ++
        BHMT R239Q —

        So, if I was taking a lot of methy folate, b-12 or methyl donors in say MSM (the first time this happened I was trying to following Ben Lynch’s protocol levels), would that suck up my folinic acid, which is poorly produced allowing the SHMT to go overboard and process the all the methyl donors? So, that even if I have MTHFS I still need to replenish the folinic acid somehow. I know you are not an expert as this, I am just trying to follow the logic as I see it. If there are other snp’s impacted or am I on the wrong track logically? BTW, I did pay $$$ an expert to answer this question she didn’t have an answer either other than go slowly on the folinic acid and never take SAMe. I got a lot of great information other wise but not this answer. I guess I am an over methylator. Any help is greatly appreciated.

        BTW, another site you may be interested in is run by William Walsh, Ph.D. called Alternative Mental Health. I believe he also has a book.

        Thanks, again.

        sal

        PS I have seen many commenters ask why their results don’t have the same snp’s as yours. 23andme changed their algorithm somewhere at the end of 2013. I had my results done in late October my husbands in December 2013. Both the results were run thru sterling’s program and he has many fewer snp’s are his report than mine. Apparently, it is the fallout of the FDA scrutinizing 23andme’s health claims.

        1. Hi Sal, thanks for that bit about the changes at 23andme. I wish I could give you a really smart answer about the SNPs, but honestly it’s way over my cognitively impaired head. I looked at all this information a couple of times and tried to pull out some basic supplements but after a year and a half of methylation support I realized, while it’s important, it’s not going to cure me.

          Why not? I can’t help but think about how comparatively healthy I was at age 15. I still had all of the same SNPs, so what changed? Well, I believe my liver filled up with toxins, stopped producing enough bile and possibly became fatty and maybe my kidneys are holding their share of toxins as well. And very certainly my colon has a quarter inch thick coating of gray rubbery sludge on it which is very likely filled with toxic bacteria. This is a long way of saying that, I’m going after the low hanging fruit because I think I could live a very happy life if I could recover the level of health I had at age 15… And when my brain starts working again, maybe I will study up on the SNPs some more!

          warm regards,
          Eric

      1. I have used this as well, it is very good. I think I paid about 45.00 for it but I believe you can run your raw data again and again to see if new information is added about SNP’s. Honestly some of these nutrients I didn’t even know existed and that they could be a problem. No to mention it cleared up a lot of my questions about why my body was one way or another.

  10. I just discovered that you have to check and make sure that each gene is reported correctly (in genegenie, so far). The rs1135840 SNP is a wild type, GG is normal, but genegenie reports it as homozygous. Interesting!! Thanks so much, all, for helping to sort through 23andMe data.

  11. Thats a great write up. I wonder if you checked all these SNPs one by one or there is any application that you can feed raw 23andMe results to get such output? I have used GeneticGenie and Nutrahacker, but none of them go this deep.
    Thanks in advance.

      1. I am about to do the same thing. Otherwise making the connections are too confusing. 🙂

  12. Thanks for such a great blog! Very helpful.

    I’m wondering if you’ve come across any ways to treat SOD2 polymorphisms. I have them, too . . .

    Antioxidants?

    1. i haven’t looked for any ways to treat SOD2 – I’m always trying to address the one issue I think is the possible source of everything else – the logjam – and I think that’s my liver now…

          1. Hi Eric

            So does one need a more extensive interpretation of their 23andme results than what genetic genie gives you? I got nowhere near as many snp results as you have above!

      1. My daughter also has SOD2 (rs2758331) ++, SOD2A16V(rs4880) ++, SOD2 (rs2758331) ++. Also many other mutations. Is it wise to take a SOD2 supplement? Or do you need to consider other mutations as well first? She also has 8 ++ mutations in the FUT2, GAD1. Any insight? She has been worn out most of her life (24).

        1. hi Paula, I looked for connections between GAD1 and the liver and didn’t find much… What are your issues?

    2. Ben lynch has a supplement called sod at seeking health.com advised to take with liposomal glutathione start slow and possibly twice a week then up if your ok I have +/+ cbs and have huge sulpher issues which glutathione is bit can handle twice a week for now. Plus supplement your electrolites mag and K helps your cells with the detox.

  13. Hi,
    I’m just starting this journey and find this so helpful. I have to say I am so confused by the enormity of this. Is the only way to make sense of this information from Genetic Genie, Sterling’s App, Livewello, and Nutrihacker to go mutation by mutation and chart it out? Does anyone have a program or consult that can do it this for me. Honestly, I don’t trust myself to get it right. I started with folinic acid and felt terrible. Finally figured it out with the info from this site that it wasn’t a good thing for me, MTHRS++ MTHFD1L++ MTHFS++ among others. Any suggestions?

    1. well, you could always pay a consultant to help you over the phone.. I don’t know who but I know some people offer the service.

  14. I do work for Dr. Amy Yasko and would like people to know about a new site , its called http://www.knowyourgenetics.com.
    You can can take your data from any lab and put them in to get Dr. Amy’s Methylation Analysis.
    Other documents are there for people to and use. Its a great tool.
    Have a great day.
    D

    1. Danielle, I was excited to learn about the site but seriously dismayed when, because it does not account for VDR Bsm at all, it gave me advice that was very wrong for me (said I needed to avoid methyl groups when I NEED them and that I should supplement with Vitamin D when I’m at toxic levels for Active D 1,25 due to the VDR Bsm defect). I hope this defect is added at some point in the future.

  15. Aha! You did get this. Awesome! FWIW, I too am VDR Bsm ++ and learned something interesting this past month. It means we’re VERY good at converting storage D (D 25 which is what Vitamin D labs typically measure) to active D (D 1,25 which they typically won’t bother measuring). This means that, for us, particularly if we supplement with Vitamin D, we need to get labs that show BOTH levels to make sure NEITHER are too high. I just had mine done and, while my storage form was in the 50s, my active form was above safe levels – over 100! Given that my doctor has been pushing Vitamin D heavily, to the point where my storage form was in the 90s at one point, if the ‘double’ ratio is a standard thing for me, I’ve probably been at toxic levels for active D for a few years now!

    Thank you so much for sharing your journey! 🙂

    1. just got my blood test results and my D 25 is at 17 – a new low for me. Going to start supplementing again and going outside without covering up… Although I’m nervous because a three-day migraine is like a small bomb in my life!

  16. Hi Eric

    I wanted to ask you something. How much of your problems do you think can be related to the 3 FUT2 mutations?

    You say you dont use among other things alcohol and caffein, can the intolerance to those be sourced back to the FUT2 genes?

    Im glad i purchased the sterling app cause I did not see the whole picture before with the other reports.

    1. hi Leon, I really wish I could give you an intelligent answer but I just have no idea. Glad you also found the Sterling app to be valuable 🙂

      be well

    2. Leon, when you say other reports, are you referring to free ones, or to Live Welo? I’ve been wanting to do something for further interpretation. I’m clueless at how to find more info and understand the 23 and me data. I’ve wondered if MTHFR.net or Live Welo would be a better route to try. Or if it’s worth spending a little more for more analysis.

      Thanks!

  17. Thanks for posting all of this, very helpful. I am wondering if you put together the assessment “Elevated Risk” in the top center of your post or did I miss something when I got my report from MTHFR?

  18. 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. 

      1. 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. 

        1. 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!

  19. 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)
     
     
     

    1. 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!

      1. It could be that since the basic building blocks of DNA, adenine (A), thymine (T), cytosine (C) and guanine (G) bond together only in specific pairs of A with T and C with G, there might be some sort of nomenclature alternative that instead of “reading” one side of the pair, reads the other. In that case, C and G would amount to the same structure, as would A and T.

        For a discussion that’s not too overly technical to understand, check out the wikipedia entry at DNA.

    2. Hello Linda,
      It is assumed by many that the minor allele is the one that is problematic, however this is not necessarily borne out by research in all cases. I have been reading through research articles on an almost daily basis for a long time and what I find is that often times the minor allele is the one that causes trouble, but not always. Sometimes it can be helpful. Often times it is a matter of how a variety of mutations/variations work together that creates an issue or provides some superb healthy aspect (It can go both ways.) It is useful to look at multiple mutations within a particular enzyme system for example as well as enzyme systems that are very dependent on each other. (Ultimately all systems are dependent on each other, but it is best to look at those that feed into each other in an intimate manner as this is where you will find the most causal relationships that matter.

  20. 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

      1. 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. 🙂

  21. 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!

  22. 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

     

     

  23. 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

    +/-

     
     
     

    1. 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.

  24. 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.
     

    1. 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?

  25. 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.

    1. 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!

      1. Hi Eric,
        Saw your comment about the frustrating nature of genetics reporting tools and we wanted to reach out to you:
        We are working hard to make sure we democratize information about genetics so users feel empowered when they have this info about themselves and we have added a lot of tools since you used us. LiveWello is unique because it gives you much more than just a 300 SNP variance report: It will give you your Gene report for 600,000 SNPs and attaches 8 resources for learning to each Gene. This is helpful because you should have all the information in your Raw Data not just some of them. That way, you and your Heallthcare Practitioner can have the benefit of all this information when creating your treatment plan. So basically, as long as a SNP is in your Raw Data with rsID and Minor Allele, Livewello will generate your Gene Report for it. Livewello is also the only Genetics Application that offers you:

        ~A free Gene library with hundreds of free Gene Reports you can use: https://livewello.com/snps/library ,

        ~A free Health Conditions tool to get your Gene Reports based on your health issues: https://livewello.com/gwasand

        ~A Sandbox tool for Customized Gene Reports https://livewello.com/snps/sandbox
        We also just added the population Genetics tool which is a graphical representation of how many other users share a mutation with you.

        With these features, we hope that it becomes the only tool a user needs to serve them throughout their journey to recovery and maintaining wellness. We have gone ahead and created 2 custom “Eric Templates” which includes all the SNPs you have mentioned in this blog post so that your readers who have 23aandMe and AncestryDNA raw data, can click on these 2 links to see their results as compared to yours:
        Eric part 1: https://livewello.com/snps/library?action=preview&index=783226&for=demo
        Eric Part 2: https://livewello.com/snps/library?action=preview&index=962556&for=demo

        Please email me and let me know any other suggestions you have.
        https://www.facebook.com/notes/livewello/about-livewellos-gene-app/863565933654629
        Access to App: https://livewello.com/snps

        1. Thanks Nancy, that’s very thoughtful and proactive of you, well done!! I hope my readers will take advantage of this:)

  26. 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

    1. 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

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