Methylation Analysis Results

Gene & VariationrsIDAllelesResult
COMT V158Mrs4680AG+/-
COMT H62Hrs4633CT+/-
COMT P199Prs769224GG-/-
VDR Bsmrs1544410CC-/-
VDR Taqrs731236AA+/+
VDR Fok-Inot foundn/an/a
MAO A R297Rrs6323T+
ACAT1-02rs3741049GG-/-
MTHFR C677Trs1801133AG+/-
MTHFR 03 P39Prs2066470GG-/-
MTHFR A1298Crs1801131TT-/-
MTR A2756Grs1805087GG+/+
MTRR A66Grs1801394AG+/-
MTRR H595Yrs10380CC-/-
MTRR K350Ars162036AG+/-
MTRR R415Trs2287780CC-/-
MTRR S257Tnot foundn/an/a
MTRR A664Ars1802059AG+/-
BHMT-01not foundn/an/a
BHMT-02rs567754CT+/-
BHMT-04rs617219AC+/-
BHMT-08rs651852CT+/-
AHCY-01rs819147TT-/-
AHCY-02rs819134AA-/-
AHCY-19rs819171TT-/-
CBS C699Trs234706AG+/-
CBS A360Ars1801181GG-/-
CBS N212Nrs2298758GG-/-
SUOX S370Snot foundn/an/a
NOS3 D298Enot foundn/an/a
SHMT1 C1420Trs1979277GG-/-

Before getting started: Understanding the basics

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. This phenomenon has been termed “epigenetics”. Researchers in the growing field of epigenetics have demonstrated that certain genes can be over- or under-expressed with certain disease processes. Researchers in this field hope that by understanding of how these genes are regulated and what is influencing them, we may be able to change their expression. Using epigenetic concepts along with a good understanding of the methylation cycle, researchers have begun to make recommendations to optimize genetic expression and help to restore health.

Disclaimer: The information on this website is for educational purposes only and should not be used a substitute for a consultation with a healthcare provider. You, the reader, are instructed to consult with a qualified healthcare provider prior to acting on any suggestions presented on this website. This information is not intended for the diagnosis, treatment or cure of disease.

MTHFR Mutations

First we’ll look at a few of your MTHFR mutations. According to research, these mutations are important and can be implicated in various disease states.

You have 1 heterozygous (yellow) mutation(s). These are generally not as bad as red homozygous mutation, but they may still worth paying attention to. They include:

  • MTHFR C677T

Now let’s move on to discuss what these MTHFR mutation(s) mean.

MTHFR C677T

One function of MTHFR (Methylenetetrahydrofolate reductase) is to help convert homocysteine to methionine. A MTHFR C677T mutation means that the MTHFR enzyme may have trouble performing its task leading to high levels of homocysteine. According to Dr. Ben Lynch, impaired function of the enzyme can cause or contribute to conditions such as Autism, Chronic Fatigue Syndrome, Fibromyalgia, Miscarriages, IBS, many birth defects, Multiple Sclerosis, Alzheimer’s, Bipolar Disorder, blood clots, Stroke, Chemical Sensitivity, and many other conditions.

MTHFR C677T can also lead to high homocysteine. You can ask your doctor to test for homocysteine levels. If you have high levels of homocysteine, it may be related to your MTHFR C677T mutation. But even if one has a (+/+) or (+/-) mutation, it does not necessarily mean that they will have high homocysteine levels.

As S-adenosylhomocysteine (SAH) accumulates, the COMT enzyme may become impaired. Inhibiting COMT can increase dopamine levels for those with COMT V158M (-/-), but for those with COMT V158M (+/+), the high level of SAH can lead to behavior problems and mood swings according to Dr. Amy Yasko.

Nutritional Support of MTHFR C677T

Supplementing with Folate (preferably as L-Methylfolate) can help alleviate the effects of MTHFR C677T as well as lower one’s homocysteine levels. There are a lot of different types of folate on the market, and I recommend reading this article by Dr. Ben Lynch about folate. It might be a good idea to avoid synthetic folic acid and folic acid fortified foods such as cereals. Also, lowering other doses of forms of folate or folinic acid may be important as it can compete with L-methylfolate.

To avoid adverse effects, one can start with very low doses of folate and work to higher doses. Side effects can occur as a detoxification effect as this pathway becomes unblocked. In the case of extreme adverse effects, time-released niacin and/or potassium may be able to stop the side effects.

All of Your Other Mutations

Now we are going to look at all of your mutations. You do not necessarily need to worry about all of these mutations, but certain mutations may cause problems in certain individuals. Genetic Genie does not look at the expression of your genes, it only looks at specific gene SNPs. Keep in mind that even if you are homozygous or heterozygous for a certain mutations, it doesn’t necessarily mean there is a problem with the functioning of that gene. You have 3 homozygous (+/+) mutations and 9 heterozygous (+/-) mutations.

Here are your homozygous mutations as indicated in your SNP gene table above (not including MTHFR):

  • VDR Taq
  • MAO-A R297R
  • MTR A2756G

Here are your heterozygous mutations as indicated in your SNP gene table above (not including MTHFR):

  • COMT V158M
  • COMT H62H
  • MTRR A66G
  • MTRR K350A
  • MTRR A664A
  • BHMT-02
  • BHMT-04
  • BHMT-08
  • CBS C699T

CBS Mutations

CBS (cystathionine beta synthase) catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine. Dr. Yasko considers addressing CBS mutations as first priority aside from addressing the gut. CBS defects are actually upregulations. This means the enzyme works too fast. In these patients, it’s common to see low levels of cystathionine and homocysteine since there is a rapid conversion to taurine. This leads to high levels of taurine and ammonia. The NOS mutation can exacerbate ammonia issues. Furthermore, addressing CBS can help lower excessive levels of taurine and help detoxify ammonia. Dr. Yasko recommends that one supports their CBS enzyme for at least 6 weeks before starting methylation supplements. When one tries to take nutrients to support their methylation cycle before addressing the CBS upregulation, all the nutrients basically lead to nowhere. Instead of generating glutathione, the supplements may deplete the rest of the cycle.

Addressing the CBS Mutation

Before one starts adding supplements, it may be a good idea to get a baseline UAA from a doctor. This will determine one’s Taurine levels. After about 4-6 weeks of following the CBS protocol (outlined in the book Autism: Pathways to Recovery), one should retest their UAA. Once one’s UAA is at 50% or below, one can add the methylation supplements. It’s important to regularly use UAA testing as taurine should remain at 50% or less. If taurine climbs one may need to address ammonia. Yucca Root and Charcoal/Magnesium flushes can help address high ammonia levels. High doses of L-Ornithine may be effective as well according to medical studies.

The CBS mutation not only leads to excess taurine, but can also lead to excess sulfur groups. For this reason, it may be a good idea to limit sulfur intake. Excess sulfur intake can trigger a stress response or chronic stress. Sulfur is normally bound to amino acids, but the CBS upregulation can instead release the sulfur groups to sulfites in the body. There are many things one may need to avoid with a CBS upregulation. Some of the items include garlic, broccoli, eggs, onions, legumes, meat, Epsom salt baths, alpha lipoic acid, glutathione, chelating agents such as DMPS, NAC, Milk Thistle, various other supplements, and much more. Please look to other sources for foods and supplements that are high in sulfur.

Supplementing with molybdenum may help as excess sulfites deplete it. Manganese is also important in ammonia detoxification. A Low protein diet can help as the body will have less ammonia to detoxify. It’s important to measure molybdenum and manganese with a minerals test before supplementing.

BH4 can also become depleted with a CBS upregulation. BH4 helps regulate neurotransmitters and mood. Other mutations, such as MTHFR A1298C, Chronic bacterial infections, and aluminum can also lead to low BH4 levels. Lack of BH4 can lead to mast cell degranulation and possibly mast cell activation disorder (MCAD). While difficult to obtain, BH4 supplementation may help in the presence of BH4 deficiency.

Other supplements that may help are Slippery elm bark for the gut. And according to Dr. Yasko Molybdenum, EDTA, carnosine, and zinc may help balance the copper/zinc ratio.

The CBS Upregulation is a complicated subject and for more info, I suggest purchasing or finding the book Autism: Pathways to Recovery. Searching for other websites or online support groups talking about the subject may be of help as well.

MTR/MTRR Mutations

MTRR (Methionine synthase reductase) helps recycle B12. The combination of MTR and MTRR mutations can deplete methyl B12. MTR A2756G, MTRR A66G, MTRR H595Y, MTRR K350A, MTRR R415T, MTRR S257T, and MTRR A664A all work together to convert homocysteine to methionine.

MTR (5-methyltetrahydrofolate-homocysteine methyltransferase) provides instructions for making the enzyme methionine synthase. Methionine synthase helps convert the amino acid homocysteine to methionine. To work properly, methionine synthase requires B12 (specifically in the form of methylcobalamin). An MTR A2756G mutation increases the activity of the MTR gene causing a greater need for B12 since the enzyme causes B12 to deplete since it is using it up at a faster rate. Mutations in MTR have been identified as the underlying cause of methylcobalamin deficiency. Megaloblastic anemia can occur as a consequence of reduce methionine synthase activity.

A homozygous mutation of MTR A2756G is relatively rare (<1%). Some studies have demonstrated that people with a combination of MTHFR C677T and MTR A2756G have persistently high homocysteine levels unless they are treated with both B12 and folate.

Nutritional support of MTR/MTRR

According to Dr. Yasko’s clinical experience, one should first take into account COMT V158M and VDR Taq status. She finds that those with COMT V158M + and VDR Taq – mutations often don’t tolerate methyl donors well. She says that those with these mutations should carefully balance their ratio of Hydroxyl B12 and Methyl B12. She often suggests low dose cyano B12, adenosyl B12, and vitamin E succinate. High dose methylcobalamin (5 mg per day and above) may be implicated and necessary with this mutation – especially if one is homozygous and/or has MTRR + mutations. The level of B12 one needs depends often depends on the number and combination of these mutations. Like everything else, one should slowly build up doses of both methylcobalamin and/or hydroxocobalamin to avoid adverse effects.

DMG and the supplement TMG also stimulate the BHMT pathway to convert homocysteine to methionine, but one should take caution if they are sensitive to methyl donors.

Patients with MTR/MTRR may also benefit from the combination of GABA and L-Theanine. L-Theanine is a methyl donor. They may also benefit from taurine, Pycnogenol® pine bark extract, and grape seed extract.

MAO-A R297R

MAO-A (Monoamine oxidase A) is a critical enzyme involved in breaking down important neurotransmitters such as serotonin, norepinephrine, and dopamine. While a homozygous (+/+) mutation is very common, prolonged periods of stress, violence, or trauma can lead to epigenetic changes that further decrease enzyme activity. On the table above, males only have one allele since the gene is inherited through from their mother since it is located on the X chromosome. Males are more likely to have this mutation, represented on the table as homozygous (+). Only females can be heterozygous (+/-) for this mutation. When a (+/+) MAO-A mutation is combined with a (+/+) or (+/-) COMT V158M mutation, one may be more prone to develop Obsessive Compulsive Disorder (OCD), mood swings, aggressive and/or violent behavior, and personality disorders. Chronic infection can deplete tryptophan stores, and this can be tested with an organic acid test (OAT) and urine amino acid tests (UAA) according to Dr. Yasko. This test may indicate high levels of 5HIAA (5-hydroxy indole acetic acid).

Nutritional support of MAO-A R297R

Dr. Yasko says that her Mood S RNA formula and 5HTP may help balance serotonin. Furthermore, she satiates that BH4 deficiency (often caused by aluminum toxicity), increased levels of ammonia, and MTHFR A1298C are all factors that can negatively impact serotonin levels.

There is not a whole lot of information out there on how to increase the activity of the enzyme. And while not nutritional, there is a product called Respen-A developed for Autism with intention of increasing MAO-A activity. Respen-A can only be obtained from a few compounding pharmacies and requires a prescription.

COMT Mutations

COMT (catechol-O-methyltransferase) helps break down certain neurotransmitters and catecholamines. These include dopamine, epinephrine, and norepinephrine. Catechol-O-methyltransferase is important to the areas of the pre-frontal cortex. This area of the brain is involved with personality, inhibition of behaviors, short-term memory, planning, abstract thinking, and emotion. COMT is also involved with metabolizing estrogens.

COMT (-/-) individuals can usually break down these neurotransmitters efficiently, but COMT (+/+) individuals may have trouble breaking these chemicals down from impaired function of the enzyme. With a COMT + status, people may have trouble with methyl donors. This can lead to irritability, hyperactivity, or abnormal behavior. They also may be more sensitive to pain.

Nutritional support of COMT mutations

Since COMT + individuals often have trouble tolerating methyl donors, they tend to do better on a combination of hydroxy B12, adenosyl B12, and/or cyano B12. Methyl B12 is usually much easier to tolerate for those that are COMT (-/-).

VDR Mutations

VDR (Vitamin D Receptor) encodes the nuclear hormone receptor for vitamin D3. Low or low normal vitamin D values are often seen in those with chronic illness and even the general population. Low vitamin D is related to a lot of neurological and immunological conditions. Vitamin D stimulates enzymes that create dopamine.

VDR Fok has been associated with blood sugar issues and poor pancreatic activity.

With COMT V158M + and a VDR Taq + status, the body may have further trouble tolerating methyl donors. VDR Taq (-/-) individuals may already have higher levels of dopamine, and it’s worth noting that combinations of variations COMT and VDR Taq can lead to a wide range of dopamine levels. Those that are VDR Taq (+/+) and COMT (-/-) may have lowest dopamine levels.

Nutritional support of VDR Mutations

Dr. Yasko advises patients to rotate methyl-containing supplements (instead of using them all daily) for those with COMT V158M + and VDR Taq (-/-).

Ginkgo biloba may increase dopamine uptake. Small doses of Mucuna Pruriens contains natural dopamine, and can be helpful for those with low dopamine.

VDR Fok + can impact vitamin D levels. Research shows that supplementing vitamin D may be beneficial. Sage and rosemary support vitamin D receptors. It may be necessary to support the pancreas when having a VDR Fok + mutation using vitamin and digestive/pancreatic enzymes.

BHMT mutations

BHMT (betaine homocysteine methyltransferase) acts as a shortcut through the methylation cycle helping convert homocysteine to methionine. The activity of the enzyme can be negatively influenced by stress. The Information on this enzyme related to methylation is mostly based on Dr. Amy Yasko’s clinical experience and research.

According to Dr. Yasko, a homozygous mutation of BHMT 01, BHMT 02, BHMT 04, can produce results similar to one with a CBS upregulation even if you don’t have a CBS upregulation. In her book, Autism: Pathways to Recovery, She also states that a BHMT 08 mutation may “increase MHPG levels relative to dopamine breakdown (HVA)”. This can result in attention type symptoms. It is common to see elevated glycine in someone with a homozygous BHMT 08 mutation.

Addressing the BHMT mutations

According to Dr. Yasko, limiting taurine for BHMT 01, 02, and 04 may be helpful, and supplementing NADH, SAMe, and DMG may help with BHMT 08 + status. According to the Heartfixer Analysis, one may bypass the dysfunctional enzymes by stimulating the BHMT pathway to convert homocysteine to methionine in several other ways. Phosphatidylcholine or phosphatidylserine can stimulate the BHMT pathway. A good quality lecithin is a good source of phosphatidylcholine (it usually comes from soy, eggs, or sunflower seed). Egg yolks are a good source of lecithin as well. TMG is also an option, but one should take caution if they are sensitive to methyl donors.

If you have a BHMT 01, BHMT 02, or BHMT 04 mutation and don’t have a CBS mutation, information about CBS was not included in your report. If you have these mutations, you can find our info about addressing the CBS upregulation at http://www.geneticgenie.org/all-mutations.

More information

For more comprehensive information, you can look at these sources: