Understanding StrateGene®

Genes
Your genes provide instructions for making proteins, which include enzymes and receptors. The word “gene” is used interchangeably for “enzyme” and “receptor” in this report and in the book, Dirty Genes.

Enzymes
Enzymes are proteins that convert one chemical into another in a biological pathway. Enzymes usually require a cofactor to help them to work correctly.

Receptors
Receptors are proteins in a cell membrane that bind with a specific neurotransmitter, hormone or other substance to trigger a preprogrammed biochemical response. They do not require a cofactor.

Compounds
The compounds that your enzymes convert range from biological chemicals that are produced by your body, vitamins and nutrients obtained from your food or supplements, or synthetic chemicals obtained from the environment. Enzymes have a role in processing them all.

Substrate
The starting or entering compound needing to be processed is referred to as the substrate and the resulting compound is known as the end product.

Cofactors
In order for the enzyme to process the substrate and convert it into an end product, the cofactor must be present. Typically, cofactors are a specific vitamin or mineral.

SNP
A SNP occurs when a nucleotide (a single base position in your DNA) is substituted for a different nucleotide within a section of your DNA that codes for a particular protein.This causes either a change in the amount of enzyme produced or a change in its ability to do its job.

Sometimes a SNP causes a minor change, but sometimes it can have a major impact. Most often a SNP reduces the ability of the enzyme to do its job. Yet sometimes the activity of an enzyme is increased by a SNP (this is the case for some COMT variants for example).

It may help to think of the pathways like a mini factory with a series of workstations.
At each workstation is an enzyme which transforms its substrate into an end product using a cofactor. The end product of this enzyme’s work then becomes the substrate for the next enzyme, which transforms it into a different end product and may use a different cofactor. This continues all along the line until the final end product is excreted out of the body or broken down completely into things like water.

Some enzymes only work on one substrate (like MTHFR). Other genes have the ability to process many different substrates typically within a specific family. MAOA, for example, processes dopamine, serotonin and norepinephrine. These are known as ‘monoamines’. COMT, SULTs, UGTs and CYPs are just a few others that process many different compounds. The speed for processing these various compounds can be very different and typically is.

Speed up or slow down
There are many other things that may cause an enzyme to speed up or to slow down. These are indicated on the pathway diagrams and explained in the text for the gene. Things that increase the speed of the enzyme are colored orange on the pathways and things that slow it down are colored purple.

Good and bad have the same effect?
Sometimes people are confused by why things that seem good and also things that seem bad have the same effect on an enzyme. Let’s take DBH (dopamine beta-hydroxylase) for example. This is the enzyme that converts dopamine into norepinephrine. We find that vitamin C and chronic stress both speed up the DBH enzyme. One is good, one is bad – what am I supposed to do? The key is in understanding why they have this effect. Vitamin C is a cofactor for DBH and therefore supports the enzyme to work faster when needed (this is good). However, chronic stress forces the enzyme to work faster in order to generate stress hormones (this is bad). Overworking anything can lead to problems.

Your aim should NOT be to increase all the things that speed up or slow down an enzyme. In the case of DBH, you may need to increase vitamin C to support DBH when needed. And long term, you should aim to decrease your chronic stress levels so that your DBH enzyme doesn’t have to work so hard. In Dirty Genes terminology, chronic stress is one of the factors that dirties your DBH gene while vitamin C and meditation cleans it. What cleans and dirties each of your genes is fully explained in the text for each gene in your StrateGene® report.

More is not better
In the case of the DBH gene, copper is a cofactor. Sufficient levels of copper are essential for DBH to do its job. However, research has found that excessive levels of copper actually reduce the ability of DBH to do its job. This is why the Dirty Genes book recommends “pulsing” supplements and “tuning in“ to how you feel. You may need to supplement for a while to bring your nutrient levels into the optimum range, but don’t just keep going. Take a break and “tune in” to how you’re feeling.

Your enzymes work in harmony
If an enzyme is working too fast it may process a substrate too quickly. This may eventually leave you with an insufficient amount of this compound. The supporting cofactor may also get used up. If a gene is working too slowly, the substrate that the enzyme processes is likely to backup. This will put pressure on other enzymes to process these compounds. This isn’t ideal as the other enzymes have their own jobs to do. If they are given the additional work of processing extra substrate they may fall behind on their usual roles and cause new problems.
Now the mini factory has a jam.

Let’s look at an example.

-Open up your StrateGene® Report and look specifically at the ‘Dopamine Pathway’. Find DOPAMINE. Now trace the black line to the right of DOPAMINE and up and over to COMT. As you can see, the gene COMT, makes the COMT enzyme which processes dopamine. Dopamine is a substrate for COMT. If COMT is working too quickly, it may deplete dopamine leading to poor focus, lack of motivation or depression. Magnesium and SAM are the cofactors for COMT. Since COMT is working too fast, both SAM and magnesium may also become deficient.

-Let’s see how a fast COMT can burden another gene. Continue following the arrows over to the right of COMT. A fast COMT processes dopamine into its end product, 3-MT. Now 3-MT becomes the substrate for MAOA. MAOA has to deal with the excessive amount of 3-MT that the fast COMT is providing. To process the 3-MT, the MAOA gene makes a lot of MAOA enzyme which uses up vitamin B2 (riboflavin).

-Let’s take it one step further. Let’s see how one pathway, such as Dopamine, impacts other pathways such as Glutathione and SAM. You can see that MAOA enzymes generate reactive oxygen species such as hydrogen peroxide (H2O2). The H2O2 uses up your precious glutathione and puts burden on the GST gene found in your Glutathione Pathway. The SAM Cycle is also impacted as COMT uses up SAM which is made, and recycled, in the SAM Pathway. This is why we cannot just look at one gene at a time. We must see the impact genes have on other genes. More importantly, we must come to realize how one pathway impacts other pathways. It takes time to understand this. You’ll get there!

-Let’s look at another scenario. If COMT is working too slowly, it puts pressure on other enzymes and ultimately may cause a build up of dopamine. This may lead to insomnia, headaches, irritability or migraines. Since COMT is not processing dopamine sufficiently, other genes and their enzymes have to step up and get the job done. The slow COMT puts an additional workload on compensating enzymes such as MAOA and DBH to handle the excess dopamine. If dopamine can’t be cleared quickly enough by these other enzymes, it may convert into the toxic quinone form.

All of what was just described can be visualized by looking at your pathways. Be sure to use your pathways a lot. The more you use them, the more comfortable you’ll get. Think of your StrateGene® pathways like a new pair of hiking boots. At first, you get blisters but once you break them in, they are so comfortable and they protect you from hurting yourself!

The key is having your genes and their respective enzymes working in harmony with each other.

Imagine a nice flow from one enzyme to another without any hiccups. A nice consistent speed moving through the pathways. In Dirty Genes terminology, if a gene is working too quickly or too slowly, it is “dirty”. But what causes a gene to become dirty? You will see in the Dirty Genes book that your genes can be born dirty, or your genes can be acting dirty due to lifestyle and environmental factors.

Your StrateGene® Report provides you the ability to determine both types of dirty genes. Born dirty genes have SNPs in them and determine your genotype. Acting dirty genes do not have SNPs in them but are behaving problematically. Acting dirty genes determine your phenotype. With practice or the support of your health professional, you’ll learn which genes are acting dirty, whether or not they were born dirty.

Let’s discuss what Born Dirty and Acting Dirty genes are and their impact on you.

Dirty is simply referring to the fact that your particular gene is acting differently than what’s typical – and that’s OK!

We are all born with thousands of single nucleotide polymorphisms in our DNA – known as SNPs for short.

SNPs occur naturally over generations and often confer an adaptation to the environment and/or a survival advantage. Problems arise when we don’t live the same lifestyle or in the same environment that our ancestors’ genes were designed for.

It is very important to understand that even if your StrateGene® report has identified a ‘born dirty’ SNP in a particular gene this DOES NOT mean that your gene is actually problematic. In other words, despite having inherited a potentially problematic genotype, it may not currently be a problem for you. If you have the right cofactors to support the gene and your pathways are flowing well, then a SNP may not actually be causing you any issue at all. This is VERY important! This is why StrateGene® does not identify SNPs with the traditional red, yellow and green coloring.

A ‘born dirty’ SNP may only demonstrate its impact on you when there is a high demand on the enzyme. Common situations which increase demand on enzymes are physical or mental stress, lack of sleep, chemical exposures or infections.

For example: Imagine you have a DAO SNP which reduces your ability to breakdown histamine in your digestive system. This SNP alone does not result in high histamine, it just reduces the amount that DAO can typically handle. Over the years, you couldn’t handle a glass of wine at all. You never understood why but you simply reduced your intake to just enjoying an ounce of wine with company. Your DAO enzyme is not pressured to work too hard with just an ounce of wine. However, if you decide to have a glass of wine, you really become irritable, red in the face and hot because your DAO enzyme is now overwhelmed. If you support your slower DAO enzyme with some supplemental DAO enzyme, you may find that you tolerate the additional wine much better.

When you look at the pathway diagrams, you may see that you have some enzymes that naturally work faster and some that naturally work more slowly. This is not good or bad – it’s just you!

An ‘acting dirty’ gene is one that is without any known SNP, yet it is acting suboptimally.Many people believe that if they do not have a SNP in a specific gene, then there is no issue in that particular gene. There definitely can be issues despite not having any SNP.For example, if someone does a genetic test and finds out that their MTHFR gene does not have any SNPs, they think their MTHFR gene is healthy. This is not the case. Their MTHFR gene may have ‘become dirty’ despite it being without any known SNPs.As with most dirty genes, born dirty or acting dirty, they can be cleaned up. Before cleaning up your dirty genes, one must understand how their genes get dirty.There are four main reasons why your genes may be acting dirty:

Most genes make enzymes. Enzymes need cofactors to help them to function. A cofactor is often a vitamin or a mineral. Most cofactors may be obtained directly from food.

Some cofactors are generated internally, such as SAM and BH4 (you will learn about these in your report). But these internally-generated cofactors are still generated by enzymes which require vitamin and mineral cofactors.

What you eat, digest and absorb needs to provide all of the necessary nutrients and cofactors for all of your enzymes to function correctly.

Supplements may provide necessary vitamins and cofactors especially during times when enzymes are working very hard – such as infections, physical or mental stress or chemical exposures. It is preferable to obtain as many nutrients as possible from the foods you eat. Supplements should only be used to ‘supplement’ the extra that you may need. Supplement literally means ‘to add to or enhance.’ Use supplements to enhance your healthy diet and lifestyle. When taking supplements, the right amount is needed otherwise the enzymes may work too fast or too slow.

See the recommendations in your StrateGene® report to see which nutrients are needed to support each of your genes.

In order for an enzyme to work correctly, it needs sufficient raw materials. You will see in the Dirty Genes book that PEMT requires sufficient choline in order to make phosphatidylcholine. If there is too little choline, PEMT is unable to carry out its function.

Similarly, if you don’t have sufficient methionine in your system, your MAT1A gene can’t convert it to SAM. SAM is the major cofactor for most of your methylation reactions, including PEMT.

However, if you consume too much methionine (from protein), this may increase homocysteine levels. High homocysteine prevents your body from using SAM. If your body cannot use SAM, then many genes are unable to function well and many symptoms and conditions result. The right amount of methionine is needed. So understanding how much protein to eat is important.

As with all things, you need to achieve a Goldilocks level – not too much and not too little.

Chemicals are all around us and inside us. We get chemicals from the 11,000 liters of air we breathe each day, the liters of water we drink, the pounds of food we eat and the countless products we touch.

Chemicals cause some enzymes to speed up, while at the same time, cause other enzymes to slow down.

For example, in the Serotonin Pathway, environmental chemicals such as pollution and pesticides have been found to block serotonin receptors. This means that your serotonin can’t do its job and you may have low mood and lack of confidence. At the same time, these same environmental chemicals cause the liver CYP450 enzymes to work faster in order to do detoxification work. This means they may not have the capacity to detoxify other chemicals.

Watch your Dirty Genes Course (found in the Education portal) for more information on synthetic chemicals and how to avoid them.

Lifestyle factors such as sleep, relaxation, exercise and stress can have huge effects on many of your enzymes. Many people focus on looking at one gene at a time. This isn’t right. One has to look at how the body functions as a complete system. This is why your StrateGene® pathways are so useful.

For example, if you live a high-pressure, stressful life, you’re stimulating your genes to make more of the stress hormones, epinephrine and norepinephrine. Now your body has all this epinephrine and norepinephrine to deal with. This puts additional pressure on your genes designed to eliminate these stress hormones. It’s a double hit. You’re using up extra substrate and cofactors to make these stress hormones. Then, on top of that, you’re using up extra substrate and cofactors to eliminate them. All this could be avoided if you reduce your stress. This is why the fundamentals of health are so important.

If you are experiencing stress, you’re using up raw materials such as tyrosine (which is also needed to make thyroid hormones) and you’re using up cofactors such as vitamin C, B vitamins and magnesium.

These substrates and cofactors are also required by hundreds of other enzymes. If the substrate and cofactors are being used up to make stress hormones, this will indirectly dirty other genes. Why? Because these other genes do not have sufficient substrate or cofactors to function properly themselves. For example, if you’re using up your tyrosine to make epinephrine and norepinephrine, then you have little left to support making thyroid hormones. Now your doctor tests your thyroid and finds that you’re hypothyroid. Giving you more thyroid hormone may help but the real support would be to reduce your stress so you can conserve your tyrosine and other nutrients so your body has what it needs when it needs it. Your genes need resources. Don’t use them all up and be sure to nourish yourself properly.

Lifestyle factors have a huge influence on whether your genes act dirty. Developing a lifestyle that is supportive to your genes is the basis of the “Soak and Scrub” protocol found in your book, Dirty Genes.

Many genes rely on cofactors produced in other pathways. We talked about this with the COMT gene above earlier. Let’s use another example as it’s very important to understand.

Look at your Histamine Pathway. The gene, HNMT (which breaks down histamine), requires an adequate supply of its cofactor S-Adenosyl Methionine (SAM). This is made in the SAM cycle. Making SAM isn’t easy. It’s common that your MTR gene, a key step in the SAM cycle to generate SAM, is dirty because it doesn’t have a sufficient supply of its cofactor, methylfolate (L-5-MTHF). L-5-MTHF is generated in the Folate Pathway by the MTHFR gene. One can be deficient in L-5-MTHF because MTHFR is dirty due to lack of riboflavin (vitamin B2).

Or your SAM cycle may have sufficient L-5-MTHF but it lacks glutathione which is made in the Glutathione Pathway. Low glutathione will dirty your MTR gene thereby preventing the production of SAM.

As a result of inadequate SAM due to these various factors, your histamine levels may go up leading to various degrees of histamine intolerance.

There’s something else you need to know. Let’s say you have adequate amounts of SAM, L-5-MTHF and glutathione, but your HNMT gene may still not eliminate histamine efficiently. This is because other genes are needed to fully process histamine. Look at your Histamine Pathway now. Find HNMT. Then look below at the downstream MAO and ALDH genes. If these two genes are slow for various reasons, you’re not able to eliminate the histamine metabolites and they accumulate, which causes feedback inhibition, and slows HNMT. The result? You’ll experience histamine intolerance even though you’ve supported your methylation. But, you have not supported your entire Histamine Pathway.

As you can see, it’s a complex system that relies on many pieces working well and in unison. This is why things like histamine intolerance are so prevalent. The good news is that once you’re aware of all these moving parts, identifying the reasons why your histamine levels are elevated is possible. How? By looking at how all the pathways and genes interact with each other. Understanding this takes time but you have the tools to help you succeed. The key is dedicating time to learning.

You’ll be rewarded as you unclog each area by cleaning your genes. Your histamine will start lowering and you’ll feel great again! You won’t even have to guess as the pathways lay it all out for you.

Use this report, in conjunction with the Dirty Genes book and course, to find out how.

The Glossary also includes lists and references to expand on the information found in your report.

Dirty gene
A gene that is acting suboptimally. It may be acting suboptimally due to a genetic SNP, diet, insufficient or excessive cofactors, too much or too little substrate, chemicals or lifestyle.

Wildtype (-/-)
The form of the DNA without any changes in amino acid sequence (i.e., without a SNP). Wildtype is usually found in the majority of the population. The symbol (-/-) indicates the wildtype version.

Heterozygous – 1 copy of a SNP
We inherit our DNA from both parents. If you inherit a “wildtype” copy of DNA from one parent and a copy containing a SNP from the other, then, this is termed “heterozygous” (Het). The symbol (+/-) or (-/+) indicates a heterozygous version.

Homozygous – 2 copies of the same SNP
If both parents happen to carry the same SNP, and you inherit two copies of the same SNP, one from each parent, then this is termed “homozygous” (Hom). The symbol (+/+) indicates the homozygous version.

rsID (also seen as rsid#)
The official number designated to identify each SNP, e.g., rs1801133 for MTHFR. It stands for “Reference SNP cluster ID number” and is used by scientists and databases to identify a unique mutation.

Alias
The common name (or nickname) for a SNP, sometimes used in research papers in place of rsid#. E.g., C677T is one alias for rs1801133 for MTHFR. They both refer to the same SNP.

Feedback Inhibition
A cellular control mechanism in which an enzyme’s activity is inhibited by the end product of the enzyme’s activity. This mechanism allows cells to regulate how much of an enzyme’s end product is produced.

ROS – Reactive Oxygen Species (ROS)
A highly reactive molecule, also known as a “free radical”, that contains oxygen. ROS cause cell damage. This is known as oxidative stress.

RNS – Reactive Nitrogen Species (RNS)
A highly reactive molecule, also known as a “free radical” that contains nitrogen. RNS causes cell damage. This is known as nitrosative stress.