Genetic Profile Report


 

THE IMPORTANCE OF METHYLATION
 

Did you ever wonder WHY all of a sudden someone develops a neurodegenerative disorder, heart disease, an autoimmune condition, suffer a stroke or even...develop cancer?

Did it just drop down out of the sky and land on their head?

No!  They expressed a “mutated gene!”

How do you express “mutated genes” like autoimmune, MS, ALS, Parkinson’s,

heart disease or cancer?

The answer is depleted methyl groups! Depletion of your body’s methyl groups is how “mutated” genes are expressed.
 

How are methyl groups in our body depleted?  By consuming a poor diet loaded with “white death”—white sugar, white flour, and white salt, “bad oils”—trans-fatty acids and hydrogenated oils, produce loaded with pesticides and herbicides, junk food, drinks loaded with caffeine, high-fructose corn syrup and acid, genetically- modified foods, and high levels of emotional stress!

Methylation is VERY important for the following processes to occur in our body:

   DNA/RNA synthesis (turning on/off genes)

   Brain chemical production (e.g. dopamine and serotonin)

   Hormonal breakdown (e.g. estrogen and testosterone)

   Creation of immune cells (e.g. NK cells and T-cells)

   Creation of protective coating on nerves (i.e. myelin formation)

   Processing of chemicals and toxins (detoxification)

   Produces Energy
 

When poor methylation occurs in our body, here is what can happen:

   Cancer

   Diabetes

   Thyroid Disorders

   Neurological Disorders…Parkinson’s, tremor disorder, MS, Alzheimer’s, dementia, peripheral neuropathy, migraines and cluster headaches

Hormonal regulation issues such as PMS, ovarian cysts, fibroids, PCOS in women or low testosterone in men

   Autoimmune disorders and Immune deficiency

   Chemical sensitivities and allergies

   Fibromyalgia

   Chronic Fatigue Syndrome

   Chronic Pain Syndromes (neck, back, shoulder, knee, etc.)

   ADHD, Autism, Asperger’s syndrome, dyslexia, and learning disabilities

   Insomnia

   Frequent Miscarriages

   Depression

   Anxiety

   Dementia/Alzheimer’s

   Lyme Disease

   Chronic Infections (Candida, parasites, bacterial, viral, etc.)

   Gut issues (IBS, Ulcerative Colitis, Crohn’s, chronic diarrhea or constipation)

   Heart Disease

   Stroke Rehabilitation



 

NOTE:  Addressing your genetic mutations or SNPs starts with addressing your lifestyle!   You need to eat an anti-inflammatory or Paleo-diet!  You need to eliminate all grains, dairy, soy, caffeine, alcohol, tobacco, and refined sugar for a minimum of 6-months!  Please see my anti-inflammatory diet for more information.

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. This report assess 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.


 

RED indicates a homozygous (+/+) mutation

YELLOW indicates a (+/-) heterozygous mutation

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 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.


 

What is a SNP?

SNP aka Single Nucleotide Polymorphism are variants that naturally occur on genes, causing changes in their functions.  Some SNPs determine characteristics such as hair, eye, and skin color. While other SNPs have functional effects on ones genes, therefore can give insight on how well your body performs key functions that can affect your health and wellness.

Disclaimer: The information on this report is for informational purposes only. This information is not intended for the diagnosis, treatment or cure of disease.

Your Specific Genetic Profile

The key is to look at your mutations that correlate to symptoms you may be expressing. “TREAT THE PATIENT, NOT THE SNP!”  The genes in your report are a starting point in supporting chronic neurological and metabolic conditions.

Key Points to Remember

You do not necessarily need to worry about all of these mutations, but certain mutations may cause problems in certain individuals.

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.

   The problem may not be the SNP/gene, but rather a cofactor or substrate.

Lifestyle and dietary changes are necessary.

The majority of the time other issues need to be addressed prior to supporting genetic mutations/SNPs from these reports.  ie.  inflammation, oxidative stress, Nitric Oxide pathways, dietary changes/restrictions, gut and other barrier system repair, blood sugar, anemias, heavy metals, toxins, infections, etc.    Just because a gene is mutated does not mean that you have a disease

or pathology.

Many of the genes in the complete report are still being research and we have limited clinical insight on some of the genes.

The goal is not to put support in for every genetic mutation/SNP in these reports.

We will come back to this report for deeper questions/layers to your health as well as for preventative options.

NutriGenomic Evaluation


 

Methylation/Methionine & Detox Pathways

PNMT

Converts norepinephrine to epinephrine (adrenaline)

□ Heterozygous

□ Homozygous

PEMT

Converts phosphatidylethanolamine to phosphatidylcholine(most abundant phospholipid)

□ Heterozygous

□ Homozygous

FOLR1

Adult Folate Receptor. Transports 5-MTHF(methylfolate) into cell

□ Heterozygous

□ Homozygous

FOLR2

Placental/Fetal Folate Receptor. Transports 5-MTHF(methylfolate) into cell

□ Heterozygous

□ Homozygous

FOLR3

Adult Folate Receptor. Transports 5-MTHF(methylfolate) into cell

□ Heterozygous

□ Homozygous

VDR Fok1/Taq1

Vitamin D Receptor. (Assess with COMT V158M SNPs)

□ Heterozygous

□ Homozygous

GAD1

Converts glutamate to GABA.

□ Heterozygous

□ Homozygous

NOS1

Nitric Oxide Synthase (Neuronal).  Associated with neurotoxicity.

□ Heterozygous

□ Homozygous

NOS2

Nitric Oxide Synthase (Inducible).

□ Heterozygous

□ Homozygous

NOS3

Nitric Oxide Synthase (Endothelial). Converts Arginine to Nitric Oxide. Autoimmunity.

□ Heterozygous

□ Homozygous

SOD1

Protects against oxidative stress and damage in the cytosol. Associated with Neurological

Disorders.

□ Heterozygous

□ Homozygous

SOD2

Protects against oxidative stress and damage in the mitochondria.

□ Heterozygous

□ Homozygous

SOD3

Protects against extracellular oxidative stress. Associated with brain and lungs.

□ Heterozygous

□ Homozygous

NQO1

Determines the effectiveness of CoQ10 in providing cellular energy and eliminating free

radicals.

□ Heterozygous

□ Homozygous

DAO

Breakdown extracellular histamine and foods.

Heterozygous

□ Homozygous

HNMT

Breakdown of intracellular histamine.

□ Heterozygous

□ Homozygous

Definition of Heterozygous -              one parent gave you the variant gene


 

Definition of Homozygous -               both patents gave you the variant gene

**This chart is a guide for nutritional support information and to reinforce systemic and metabolic heath and is not intended as a diagnosis or treatment for any symptoms, conditions or disease.

The Methylation Pathway





 

Explanation of Important SNP’s


 

MTHFR (Methylenetetrahydrofolate Reductase)

This is the popular enzyme that is responsible for the conversion of 5,10- methylenetetrahydrofolate to 5-methyltetrahydrofolate. This is an important step in the conversion of homocysteine to methionine and uses methyl B12 and methyl folate.

There are two key MTHFR polymorphisms – A1298C and C677T. The effect these have on the methylation cycle and overall health are different between the two.

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, Migraines, Miscarriages, IBS, Multiple Sclerosis, Alzheimer's, Bipolar Disorder, blood clots, Stroke, Chemical Sensitivity, increase in heart disease, peripheral neuropathy,

placental vascular problems (stillbirth), preeclampsia, neural tube defects, cleft lip and many other conditions.  MTHFR C677T can also lead to high homocysteine. High levels of homocysteine can be related to MTHFR C677Tmutations.

Elevated homocysteine is a major risk factor for heart disease and neurodegenerative states such as Alzheimer’s disease.  While homozygous (+/+) or heterozygous (+/-) mutations indicates reduced activity of this enzyme, it does not necessarily mean there will be high homocysteine levels in a clinical setting.

A1298C SNP’s do not lead to elevated homocysteine but instead play an important role in neurotransmitter function. The A1298C mutation is associated with a second set of problems: depression, anxiety, irritable bowel syndrome, fibromyalgia, chronic fatigue, migraines, dementia, nerve pain, schizophrenia, Parkinson's, tetrahydrobiopterin (BH4) problems. The 1298C is important in the conversion of BH2 to BH4 which plays a huge role in mood regulation and addictive behavior.

THE MTHFR GENE DEFECT

In 2003, a genetic study called the Human Genome Project was completed. And via that study, they discovered that an important gene towards your health and well-being called the methylenetetrahydrofolate reductase (MTHFR) was defective in a lot of folks especially those people suffering from chronic health conditions!

What a healthy MTHFR gene does for you

When it’s all working right, the MTHFR gene begins a multi-step chemical breakdown process, aka methylation, which in simplified terms, is like this:

   The MTHFR gene produces the MTHFR enzyme.

The MTHFR enzyme works with the folate vitamins (B9, folic acid), breaking it down from 5,10-methylenetetrahydrofolate to 5- methyltetrahydrofolate

5-methyltetrahydrofolate helps convert the amino acid homocysteine down to another essential amino acid, methionine, which is used by your body to make proteins, utilize antioxidants, and to assist your liver to process fats. Methionine helps with depression and even inflammation. It also helps convert estradiol (E2) into estriol (E3)!

   Methionine is converted in your liver into SAM-e (s-adenosylmethionine),

which is anti-inflammatory, supports your immune system, helps produce the breakdown of your brain chemicals serotonin, dopamine and melatonin.  It is also involved in the growth, repair, and maintenance of your cells.

   i.e. a proper methylation pathway like the above is going to mean you will

have a better chance in eliminating toxins and heavy metals, which can reduce your risk for cancer and other health issues, and put less stress on your adrenals.

What a defective (mutated) MTHFR gene does to you

It produces a defective MTHFR enzyme of different varieties i.e. it functions less than optimally, such as performing at only 40% of its capacity, or 70% of its capacity. It can mean you won’t break down toxins or heavy metals well i.e. you could find yourself with high iron, or high copper, or high mercury….etc. High copper can also cause low iron.

The defective enzyme doesn’t break down folate vitamins properly (of which folic acid is the precursor to), which can cause high homocysteine, which can increase your risk of coronary heart disease (arteriosclerotic vascular disease or venous thrombosis), and related heart and BP conditions, as well as increasing your risk for dementia.

Homocysteine is poorly converted to glutathione, which is your body’s chief antioxidant and detoxifier. You are then more susceptible to stress and toxin buildup.

Homocysteine is poorly converted to methionine, and less methionine can raise your risk of arteriosclerosis, fatty liver degenerative disease, anemia, increased inflammation, increased free radical damage… and

produce less SAM-e

    Less SAM-e can increase depression

And more broadly, an MTHFR defect can increase your risk of a variety of autoimmune disorders, cancers (including breast and prostate cancer), stroke, heart problems, congenital defects, anxiety and/or depression, diabetes, IBS (irritable bowel syndrome), miscarriages, migraines,

chemical sensitivities, thyroid issues, fibromyalgia, chronic pain, peripheral neuropathy, and many other conditions.

You can find yourself with high folate or high B12. i.e. your body will have problems converting inactive forms of folate and B12 to the active forms. So the inactive folate or B12 will simply build up in your serum, also inhibiting the active forms. Most serum folate tests are actually measuring folic acid, which needed to be converted to methylfolate to be used metabolically.

The journal Molecular Psychiatry states that “Schizophrenia-like syndromes, bipolar disorder, Parkinson’s disease, Alzheimer’s disease and vascular dementia have all been associated with one or more mutations of the MTHFR gene”.  (2006;11, 352–360)


 

More than one mutation of the MTHFR gene

Genes are passed down by your mother and your father. Most literature states there are a good 40-50 different mutations of this important gene which could be passed down by one, or both or your parents. But only two are particularly problematic: mutations on the points at C677T and A1298C. The numbers refer to their location on the MTHFR gene. You will also sometimes just see them written as just 677 and 1298.

There are many combinations of MTHFR:


 

Homozygous: means you have both copies of either the 677 mutation, or the 1298 mutation, one from from each parent.

Heterozygous: means you have one copy of either the 677 mutation, or the 1298 mutation, plus a normal one from the other parent.

    Compound Heterozygous: means you have one copy of the 677 mutation

from one parent and one copy of the 1298 mutation from the other parent.

    Triple homozygous mutations (more rare): an example would be one

C677T, one A1298C, and a P39P or R594Q, for example.

Here are possible combinations:

   Normal/Normal for both 677 and 1298

   Heterozygous 1298 / Normal 677 (i.e. one parent passed down a single

1298 mutation)

Homozygous 1298 / Normal 677 (i.e. both parents passed down the 1298 mutation)

   Heterozygous 677 / Normal 1298 (i.e. one parent passed down a single

677 mutation)

Homozygous 677 / Normal 1298 (i.e. both parents passed down the 677 mutation)

Heterozygous 677 / Homozygous 1298 (one parent passed down the 677 mutation; both passed down the 1298)

   Homozygous 677 / Heterozygous 1298 (both parents passed down the

677 mutation; one passed down the 1298)

Heterozygous 677 / Heterozygous 1298  (Compound Heterozygous: one parent passed 677; one passed 1298)

Homozygous 677 / Homozygous 1298  (Compound Homozygous, meaning you have two 677, two 1298)

High Copper/Low Zinc

This can be a common finding when you have an MTHFR defect–a high level of the neurotransmitter copper, which will conversely mean your zinc levels will fall. And since the ratio of these two metals is highly important, correctly the problem is crucial, since high copper can be related to hyperactivity, depression, headaches, acne, frequent colds due to lowered immunity, sensitive skin and/or bruising, worsening hypothyroid, adrenal stress and more.

High copper can also make it difficult to raise iron levels, including your ferritin.

Vitamin C is known to help lower high levels of copper via detoxing, but patients report they need to go low and slow to tolerate the detoxing. Zinc is also used the same way–to encourage the lowering of copper, but the same caution with detoxing applies. Lawrence Wilson, MD recommends a nutritional approach to correcting the imbalance: remove IUD’s, avoid high copper foods like chocolate, seeds and avocados, avoid stress and more.


 

SHMT (Serine Hydroxymethyltransferase)

Converts serine and THF to glycine and 5,10 methylenetetrahydrofolate.  SHMT helps to shift the emphasis of the methylation cycle toward the building blocks needed for new DNA synthesis and away from the processing of homocysteine

to methionine.  Mutations in this gene can interfere with the fragile balance of the methylation cycle. This can lead to elevations in homocysteine and imbalances in other intermediates in the body.

MTR & MTRR (Methionine Synthase & Methionine Synthase Reductase) This is methionine synthase and methionine synthase reductase and these work together and are responsible for the regeneration of methyl B12.  This is a critical part of converting homocysteine to methionine. MTRR helps to recycle B12 for use by MTR.

MTR helps produce methionine from homocysteine by remethylating cobalamin (B12) with MTHFR.   A mutation here causes increase function and increased methyl group depletion. This can be made worse by MTRR mutations. Individuals with a homozygous MTR are often low in lithium.  Lithium not only plays a role in mood, glutamate control and limiting aggression, but also has been shown to be involved in B12 transport. Many adults as well as individuals who are MTR A2756C + tend to have lower levels of lithium as judged by hair metal analysis (HMT).

MTRR is needed to regenerate Methyl-B12 for use by MTR. Mutations can cause a shortage, suggesting a need for more B12.

Mutations in this gene grouping leads to methyl group depletion as the morphed enzyme is using up B12 at a faster rate. Individuals with a heterozygous variant may benefit from supplemental methyl B12 and those with a homozygous most likely will need high doses of methyl B12.

BHMT (Betaine-Homocysteine Methylatranserase)

The product the BHMT gene is central to the ‘short cut’ through the methylation cycle, again helping to convert homocysteine to methionine. This is an enzyme that transfers a methyl group from betaine to homocysteine which produces methionine. This enzyme is found in the liver and kidney and is also involved in the choline oxidation processes. The activity of this gene product can be affected by stress, by cortisol levels and may play a role in ADD/ADHD by affecting norepinephrine levels. BHMT-02 and BHMT-04 play a role in the gut

environment. BHMT-08 is related to the impact that psychological stress has on a patient's attention levels.

AHCY (Adenosylhomocysteinase)

This is an enzyme that breaks down methionine by converting S- adenosylhomocysteinase (SAH) into homocysteine. AdoHcy hydrolysis serves not only to sustain the flux of methionine sulfur toward cysteine, but is believed also to play a critical role in the regulation of biologic methylations. This is a key

reaction that regulates the methylation of other compounds. Decreased activity of this enzyme leads to lower homocysteine levels.  This pathway is key to look at

in relation to CBS upregulations. A mutated AHCY may partially mitigate the effects of CBS upregulations and lead to taurine levels remaining moderate

rather than elevated. Individuals with a homozygous mutation will most likely benefit from SAMe supplementation.

CBS (Cystathionine Beta-Synthase)

This is which is an enzyme responsible for converting serine and homocysteine into cystothionine. This is the first step of the transsulfuration pathway and it is B6 dependent and a key part of glutathione production.  CBS defects can be upregulations where the enzyme works too fast which results in low levels of cystathionine and homocysteine and high taurine and ammonia. If there is an NOS mutation along with the CBS it can dramatically elevate ammonia

levels. Individuals with a CBS mutation will produce more sulfur end products from the methylation cycle, thus putting a burden on SUOX enzymes.  Those with a homozygous variant will most likely need to limit their intake of sulfur containing foods as they will elevate ammonia levels. This mutation can also affect a key enzyme called G6PDH in an indirect manner. This leads to altered blood sugar metabolism, red blood cell formation and blood vessel stability. This can contribute to easy brusing, bleeding and broken blood vessels. Without normalized transsulfuration the body is unable to produce adequate glutathione.

SUOX (Sulfite Oxidase)

This is a mitochondrial enzyme that is responsible for oxidizing sulfites to sulfates. This gene product helps to detoxify sulfites in the body.  Sulfites are a natural byproduct of the methylation cycle and are also ingested from foods. Sulfites are also used in food processing to reduce the discoloration of light- colored fruits and veggies and to inhibit the growth of microorganisms in fermented foods like wine and dough. They are also commonly used to prevent black spots on shrimp and lobster. They can also be found in certain medications to maintain stability and potency.  SUOX gene variants will not be able to process sulfur rich foods and sulfites well and should be on low-sulfur diets. For homozygous individuals they could have extreme reactions including severe asthma attacks. Sulfites can cause chest tightness, nausea, hives and difficulty breathing. This mutation may also be a risk factor for certain types of cancer including leukemia. SUOX function can be made worse with CBS and NOS mutations.

GSTP1 (Glutathione S-Transferase)

This enzyme is key in the detoxification processes with reduced glutathione. It also plays a key function in the metabolism of xenobiotics (antibiotics, medications, pollutants) which play a role in the development of cancers and other diseases.

MAO A (Monoamine Oxidase A)

This compound functions in the liver and nervous system. Its main role in the liver is to detoxify biological and xenobiotic amines. In the nervous system it degrades (breakdown of) neurotransmitters and in particular serotonin.

Imbalances in serotonin levels have been associated with depression, aggression, anxiety, and OCD behavior.  MAO A is inherited with the X chromosome and is considered a dependent trait so it may not show standard inheritance characteristics in males. The X chromosome in males only comes from the mother so the father’s MAO A mutations would not play a role in the son’s MAO status. This enzyme requires B2 (riboflavin) in sufficient levels to function normally. Mutations are associated with mood swings, aggressive behavior, depression, anxiety, OCD and intolerance of methylfolate (which increases neurotransmitters that can't be broken down by MAO A, causing feelings of overstimulation).  MAO A is also needed for the breakdown of intracellular histamine.  ACE deletions will also increase anxiety and lower frustration thresholds.

MAO B (Monoamine Oxidase B)

This compound functions in the blood platelets and nervous system. In the nervous system it degrades or breaks down neurotransmitters and in particular dopamine. Imbalances in dopamine levels have been associated with depression, substance abuse, ADHD/ADD, and movement disorders such as Parkinson’s.

COMT (Catechol-O-Methyltransferase)

COMT has a very important role in the nervous system as it helps to break down catecholamine neurotransmitters such as dopamine, epinephrine and norepinephrine.  There is an association between the ratio of dopamine to epinephrine and norepinephrine and individuals with ADHD. A defect will cause higher dopamine due to slower breakdown which is common in ADD/ADHD. More susceptible to dopamine fluctuations, therefore mood swings.  Dopamine levels are also critical in conditions such as Parkinson’s disease.

This has important functions in the cells of the nervous system, liver, kidneys and red blood cells. In the liver it helps to inactivate 2 & 4-hydroxyestradiols and catecholamine hormones prior to bile excretion.

COMT – V158M/H62H can have effects on prefrontal cortex processing and especially with mood and pain tolerance. The homozygous variant is associated with deviations in thought processes common in people with schizophrenia, inhibition of behavior and attention. It is also thought to be a risk factor for bipolar, panic, anxiety, obsessive compulsive disorders, eating disorders and ADHD.  Individuals with a homozygous mutation are unable to effectively metabolize dopamine, epinephrine and norepinephrine effectively. This sluggish breakdown can be a good effect as it preserves methyl donors in their brain chemistry. However, these individuals have to be careful with methyl donor

supplementation as it is known to drive up these excitatory neurotransmitters and lead too hyperactivity, irritability and erratic behavior.  As S- adenosylhomocysteine (SAH) accumulates, the COMT enzyme may become impaired. Inhibition of COMT can increase dopamine levels in COMT V158M (-/-

), but for those with COMT V158M (+/+), the high level of SAH can lead to

behavior problems and mood swings.  People without COMT mutations are generally more even tempered.

PNMT (Phenylethanolamine N-Methyltransferase)

This enzyme is the last step of the catecholamine pathway and converts or methylates norepinephrine to from epinephrine (adrenaline). This gene plays a key role the regulation of epinephrine production

PEMT (Phosphatidylethanolamine N-Methyltransferase)

This enzyme coverts phosphatidylethanolamine to phosphatidylcholine through methylation in the liver. Phosphatidylcholine is the most abundant phospholipid and is needed to make up the outer membrane of cells.

FOLR1 ( Folate Receptor 1 - Adult)

A folate receptor’s function is to bind folic acid and its reduced forms and transport 5-methyltetrahydrofolate into cells. Mutations in this gene have been associated with neurodegeneration.

FOLR2 ( Folate Receptor 2 - Fetal)

A folate receptor’s function is to bind folic acid and its reduced forms and transport 5-methyltetrahydrofolate into cells. It has been labeled Fetal due to being originally thought to be only found in the placenta, but has been also found to exist in other tissues.  Mutations in this gene have been associated with rheumatoid arthritis.

FOLR3 ( Folate Receptor 3)

A folate receptor’s function is to bind folic acid and its reduced forms and transport 5-methyltetrahydrofolate into cells. Mutations in this gene have been associated with hematopoietic malignancies.

VDR (Vitamin D Receptor)

This is the key vitamin D receptor that binds 1, 25 di-hydroxy vitamin D to activate the key signaling molecule. Vitamin D has an important role in a 3rd of the human genome. This includes immune activation, coordination and balance. It also plays an essential role in xenobiotic detoxification, calcium metabolism and brain development.  VDR Fok is involved with Blood sugar regulation.  VDR

mutations oppose COMT mutations in the regulation of dopamine levels.  A VDR mutation means that a person is less sensitive to methyl group supplement levels.  A VDR mutation can result in behaviors opposite to a COMT mutation.

GAD1 (Glutamate Decarboxylase 1)

This gene converts glutamic acid to gamma-aminobutyric acid (GABA) and has been identified as a playing a major role in insulin-dependent diabetes. Mutations in this enzyme have also been shown to lead to seizure disorders

NOS (Nitric Oxide Synthase)

Helps in the formation of nitric oxide which has a role in ammonia detoxification, oxidative stress, vascular relaxation and chemical production. NOS variants play a role in the bodies ability to handle oxidative stress which can lead to

mitochondrial dysfunction and accelerated aging and chronic disease development. NOS enzymes are necessary to convert arginine to Nitric Oxide. Those who have a homozygous variant have a reduced activity of this enzyme. NOS mutations will have an additive effect with CBS upregulations. This will lead to dramatically increased ammonia levels which can result in major health issues. In addition, an MTHFR A1298C homozygous gene may put an additional burden on proper urea cycle function. A mutation here is also made worse by a lack of mutations in SUOX.

There are 3 NOS enzymes:

   NOS1 (Neuronal) – associated with neurotoxicity

NOS2 (Inducible) – associated with tissue damage, especially to the cardiovascular system

   NOS3 (Endothelial) – associated with autoimmunity

SOD1 (Superoxide Dismutase 1, Soluble)

This gene binds copper and zinc and is responsible for destroying superoxide radicals in the body which are toxic to biological systems.  SODs are antioxidant enzymes that breakdown superoxide radicals into hydrogen peroxide and oxygen.  SOD1 enzymes protect against oxidative stress and damage in the cytosol. Mutations in this enzyme have been associated with ALS and other neurological disorders; and eye, brain and endocrine abnormalities.

SOD2 (Superoxide Dismutase 2, Mitochondrial)

This gene is responsible for destroying superoxide radicals in the body which are toxic to biological systems.  SODs are antioxidant enzymes that breakdown superoxide radicals into hydrogen peroxide and oxygen.  SOD2 enzymes protect against oxidative stress and damage in the mitochondrial. Mutations in this enzyme have been associated idiopathic cardiomyopathy, premature aging, motor neuron disease, and cancer.

SOD3 (Superoxide Dismutase 3, Extracellular)

This gene is responsible for destroying superoxide radicals in the body which are toxic to biological systems. SODs are antioxidant enzymes that breakdown superoxide radicals into hydrogen peroxide and oxygen.  SOD3 enzymes protect the extracellular space against oxidative stress and damage. Mutations in this enzyme have been associated keratopathy (graying of the cornea in the eye) and interstitial pneumonia.

NQO1 (NAD(P)H Dehydrogenase, Quinone 1)

The NQO1 gene determines which form of CoQ10, either ubiquinone or ubiquinol, your body uses most efficiently to help eliminate free radicals and provide cellular energy.  CoQ10 is a powerful antioxidant and is also critical for the production of energy in every cell in the body, especially the heart and is also needed for cognitive function and memory, mitochondrial function, and nerve health. When ubiquinone is ingested from food or supplements the body quickly

transforms it into ubiquinol. The NQO1 gene encodes enzymes that make this conversion.  A SNP or mutation in the NQO1 gene will decrease the ability of the conversion of the inactive form of CoQ10 (ubiquinone) to the active form of CoQ10 (ubiquinol).  Assessment of NQO1 genetic SNP’s or mutations can help better determine the form or forms of CoQ10 an individual needs to supplement with for optimal health.

DAO (D-Amino-Acid Oxidase)

DAO is a major enzyme involved in (extracellular) histamine metabolism especially in the digestive tract.  Mutations in DAO enzymes are associated with Small Intestinal Bacterial Overgrowth (SIBO), Leaky Gut Syndrome, multiple food allergies and sensitivities.  Other symptoms of histamine intolerance include: headaches/migraines, insomnia, dizziness/vertigo, anxiety, stomach discomfort, nasal congestion/sneezing, abnormal menstrual cycle, fatigue, edema/swelling, and skin reactions such as hives.

HNMT (Histamine N-Methyltransferase)

This enzyme inactivates histamine through methylation. HNMT plays an important role in degrading histamine and in regulating the airway response to histamine. Mutations in this enzyme have been associated with asthma.

Additional Key Terms to Know

To keep it simple the end goal of methylation and assessing genes that make the enzymes in this report is to make 2 things – Glutathione and SAM. This results

in antioxidant and methyl donors for the body to function at its optimal state and lessening symptoms from chronic neurological and metabolic disorders.

What is Glutathione?

Glutathione (GSH) is a tripetide thiol (sulfur-containing) compound molecule that is made inside every cell in the human body. It is composed of the three amino acids L-glutamine, L-cysteine and L-glycine, and is found in the highest levels in the liver, eyes, spleen, pancreas and kidneys. Glutathione is the single most protective antioxidant produced by the body and therefore the most important as it protects cells against the oxidative stress of free radicals. Thus, it protects vulnerable DNA from damage, while helping to bind heavy metals, remove toxins and enhance immune function; it is also especially supportive during viral infections.  Glutathione is also very crucial for proper mitochondrial function and energy production. Chronic illness as well as long term toxic exposure can not

only deplete stores of glutathione but also inhibit its production. The body’s ability to make glutathione declines with age. In order to correct depleted states, supplementation is necessary and can be optimized with various forms of GSH and its precursors based on an individual’s needs. While IV glutathione administration is the most effective at raising blood levels of GSH, it is also the most expensive and inconvenient. In addition, current research shows that IV

glutathione is not the best way to increase intracellular levels of GSH in most cells.  Studies have shown that plasma GSH increases post-oral GSH supplementation, which may be the result of a combination of intact absorption of GSH, absorption of its three amino acid precursors and/or systemic sparing of GSH due to increased GSH in intestinal cells.

Benefits of Glutathione

   Reduces free radical-induced oxidative stress

Helps optimize glutathione-dependent hepatic detoxification pathways, including the enhancement of heavy metal clearance

   Supports immune function

   Antiviral

What is SAMe or S-Adenosylmethionine?

SAMe is a naturally occurring compound found in the human body as well as in plant and animal foods. It is made from the amino acid methionine and is

involved in many critical processes throughout the body. SAMe is the most active of all methyl donors and has been compared to ATP in its importance for the body. SAMe plays a role in supporting the immune system and maintaining cell membranes, the protective barrier that surrounds all cells. It also helps to

produce brain chemicals such as melatonin – the hormone that helps with your

body’ sleep cycle, and serotonin – the hormone that affects your mood.

Even if the body is producing normal or average levels of SAMe, certain situations create an increased demand for it, such as:

   Aging

   Dietary deficiency

   Inflammatory states

   Emotional or physical stress

Genetic variations

Low levels of SAMe may be due to insufficient amounts of methionine. This is sometimes seen in vegetarianism or individuals with poor protein intake, as methionine is found in protein-rich foods such as such as fish, meat and dairy products.

Benefits of SAMe

Brain and mood support – helps produce brain neurotransmitters. It has been found that proper levels of SAMe are necessary to maintain healthy mood and brain function.

Liver support – protects from effects of alcohol and certain medications (i.e., acetaminophen), and supports detoxification (the removal of toxic substances from the body)

   Joint support - helpful in supporting the health of cartilage in joints, and in

managing the body’s natural inflammatory response

SAMe is also the source of methyl groups inside the nucleus for DNA methylation, which controls gene expression and masking of genetic damage. Even if the body is producing normal or average levels of SAMe, certain physiological states create an increased demand for it, such as aging, dietary deficiency, inflammatory states, emotional/physical stress or genetic polymorphisms.  Suboptimal levels of SAMe in some individuals may be due to insufficient amounts of the precursor amino acid methionine (i.e., vegetarianism or poor protein intake). Age-related decline in enzyme efficiencies throughout the body can be improved by increasing the supply of enzyme cofactors such as SAMe, B vitamins, and magnesium.

Research-proven benefits of SAMe

Brain

   Alleviates depression and cognitive deficit

   Appetite reduction

   Improves neurotransmitter synthesis and receptor binding

Inflammation & Pain

   Reduces TNF-alpha

   Reduces fibromyalgia pain

   Reduces joint damage

Joint regeneration in osteo & rheumatoid arthritis due to increased chondrocyte numbers

Liver

   Liver protection from toxins, drugs and alcohol

   Alleviates:

o Hepatitis o Cirrhosis o Fibrosis

   Increases liver glutathione levels

SAMe and the Brain

Inadequate levels of SAMe in tissues, plasma and cerebral spinal fluid have been

found to be highly correlated with conditions such as depression, Alzheimer’s,

and dementia. This could be partly due to the fact that SAMe is involved in:

   Synthesis of neurotransmitters (serotonin, dopamine, epinephrine)

Synthesis of brain cell membrane phospholipids: phosphatidylcholine and serine

   Improving neurotransmitter binding to receptors

Improving the sleep quality through its cofactor role in the synthesis of melatonin SAMe has been found clinically to be as effective as tricyclic antidepressants in alleviating depression at doses of 200 - 1600mg/day and slowing the cognitive decline associated with senile dementia. A side effect of SAMe was found to be appetite suppression.

SAMe and the Liver

SAMe was shown to improve liver function and provide protection from the hepatotoxic effects of medications (i.e., acetaminophen), alcohol, and other toxins. It increases synthesis of glutathione, and it is a precursor of taurine and phosphatidylcholine, which are essential in detoxification pathways. These functions of SAMe could potentially be helpful for women taking HRT or BCPs, and those suffering from cholestasis and heavy metal toxicity.

SAMe and the Joints

SAMe was found very helpful in preventing and reversing the damage caused by both osteo and rheumatoid arthritis through the following mechanisms:

Regeneration of the joint tissues by increasing the number of chondrocyte cells which are responsible for the production of the collagen matrix, proteoglycans and chondroitin sulfate

   Counter acts the destructive effect of the inflammatory cytokine TNF-alpha

Allowing for the synthesis of chondroitin sulfate via supplementation of SAMe may make more sense than trying to supplement chondroitin sulfate, which is a large and difficult to absorb molecule. Many of the quality studies supporting

the use of chondroitin sulfate were conducted with intravenous administration.

In addition, by improving serotonin levels, SAMe might improve pain tolerance in patients with fibromyalgia and other pain disorders.

+++Credit Source… SNPedia.com, GeneCards.com, DesignsforHealth.com, Stop Thyroid

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