Next, we have our sulfation section. These are the SUL2A1 genes. This is another detoxification gene. We have another section here known as estrogen metabolism genetics. I created this section several years ago and added to it recently because it provides some insight into some of the important genes that regulate the ability to make estrogen, as well as metabolize estrogen. We see that UGT1A1 variant is in there. We also have a glutathione transfer ACE gene in there because that’s involved in the detoxification of estrogen. We have the CYP19A1 variants, which she’s showing here homozygous 4. Now, that is a gene that codes for an enzymatic process known as aromatase. Aromatase converts testosterone into estrogen.
That can be relevant if a person has high estrogen levels. It’s also interesting to think about how these gene configurations can be playing out. What if she had the UGT1A1 variant and the CYP19A1 variant? That could mean she has significantly higher estrogen activity. It’s always good to check what the blood or, in this case, I would use a urinary hormone test to determine that. Some of these other variants could be significant. The cytochromes that are making some of these metabolites of estrogen, like the 16-hydroxy and the 4-hydroxy estrogen. COMT is what is methylating your estrogen, breaking it down. Here’s the section that was added a recently. I’m really interested about it. This is the fatty acid and lipid metabolism section.
PEMT is a gene known as phosphatidylethanolamine N-methyltransferase. What it’s doing is it’s converting the phospholipid ethanolamine into the phospholipid choline. Now, this is significant because these compounds are important for every cell of the body. Every cell membrane is comprised of choline. Your liver needs choline to make bile acids also. She’s homozygous for one of these variants here. Then we have the CHAT gene. Just to talk about that, that’s choline acetyltransferase. That is the gene that makes… It takes the choline and it makes acetylcholine, which is a neurotransmitter that is used by the body. It’s used by the vagus nerve actually as the primary neurotransmitter.
The research literature cites that the genotype GG for these CHAT genes could be associated with or are associated with Alzheimer’s disease. The reason they study that probably is because Alzheimer’s disease features lower levels of acetylcholine and that’s why the primary drugs they give the patients are cholinesterase inhibitors. That’s the CHAT gene. This is another section that’s really, really significant. I added this section recently. These are the FADS genes, fatty acid desaturase one and two. what you need to know is that every cell membrane of the human body is comprised of fatty acids and different lipids. As we mentioned, choline is one of these phosphocholine, but you also have omega-6 and omega-3 fatty acids in the cell membranes.
As I mentioned, there are really good studies that show associations between certain genotypes and then some biomarkers, some blood marker that is higher or lower with a particular genotype. Those are really relevant and important studies because it gives you something to look at and to identify, to track it, and to monitor it over time. Fatty acid desaturase codes for this variant. This 174537 variant has been studied in many studies and has shown consistently the same thing that the genotype GG is associated with higher levels of the omega-6 fatty acid, arachidonic acid. Basically what it’s doing is it’s converting the linoleic acid into arachidonic acid. It’s hyper converting that.
They actually recently looked at other studies that showed… Other studies looked at how the downstream metabolites are affected by this. More inflammatory processes like [inaudible 00:04:39] before it get produced is a result of that pathway, of that genotype. Now, that can be really significant because when you talk about arachidonic acid, you’re talking about some of the fundamental primary mechanisms of how the body makes inflammatory activity, creates it. The immune cells oxidize the the arachidonic acid through the phospholipase A2 enzyme. Then voila, you’ve got your PG2 prostoglandins. In autoimmune conditions, in pain syndromes, arachidonic acid is a big player.
It turns out she has a lot of pain and endometriosis going on. It could really be significant. Now, the good news is that this gene can be tracked. The expression of this gene can be tracked. You can look at a red blood cell fatty acid test to get the assessment of how was the marker on there, the AA to EPA ratio or arachidonic acid to EPA ratio. More often than not, I see that these people with this genotype have higher levels of arachidonic acid in their red blood cells, but the good news is that that can be modulated therapeutically with the fatty acid EPA, which is the omega-6 fatty acid. Eicosapentaenoic acid, not DHA, but EPA, inhibits this enzyme that produces excessive arachidonic acid. That’s one of the ways that EPA is antiinflammatory.
That could be really relevant if somebody has pain syndromes or Parkinson’s or Alzheimer’s or autoimmune disease or something like that that suggests chronic inflammation. This is a really significant geno set and it’s this variant, the 174537, is really relevant. Here we have a GI health genetic section and notably here is the FUT2 gene. This is the fucosyltransferase. It’s also known as the nonsecretor genotype. What you need to understand is that people that have this variant, they may have lower levels of bifidobacterium in their gut it. What it means is that they don’t secrete the blood antigen, blood type antigen, into their mucosal fluids.
What this does is this affect how the immune system responds to different bacteria and different microbes that are in the body at the mucosal level. The mucosal defenses are weaker. I believe I read one study that said that the people that are nonsecretors, they tend to be weaker at the mucosal layer, at the level, from the immune system perspective, but they fight the infection better in the blood or in the body. There’s always some pro or con about having a particular genotype, but because the nonsecretor has lower bifido levels, that could be significant because bifidobacterium is a really important probiotic bacteria in the gut. The next section is the heart health genetics section.
We’re looking at some variety of different snips related to that. I often pay attention to the NOS3, which is the endothelial nitric oxide synthase. As you see, she’s heterozygous here. You want to always kind of look for is there a family history of heart health problems or cardiovascular disease because nitric oxide synthase is important for dilating the blood vessels. Heterozygosity not usually is concerned with it. Then we have, just kind of bringing up the rear, the MTHFR variants, 1298 and 677. Generally, I found clinically that when you’re compound heterozygous, meaning that if your plus minus for both of these together, that usually from my experience suggests more higher homocysteine levels.
Homocysteine is kind of an oxidized waste product of the methylation cycle and it’s associated with cardiovascular disease. It’s actually one of the independent risk factors of heart disease. Again, it’s a biomarker that can be tracked. If the homocysteine level is higher than 10, I usually pay attention to it. Obviously with nutritional supplementation, you can lower that to some extent, getting it into a range that’s more appreciable. Next, we have some of the immune-related genetics sections. None of this is diagnostic for any disease. You can’t do diagnose celiac simply based on a gene test. It’s the only one criteria. One section that was added recently is the TGF-beta section, transforming growth factor beta.
This is a immune cytokine, and it plays an important role in immune cell signaling. The genotype here is associated with higher levels of TGF-beta, which is a… It’s both pro and antiinflammatory. But we also see that the FOXP3 transcription factor is plus plus here. That’s like the lock and key for the TGF-beta. It allows the TGF-beta to be expressed. We also see the interleukin-2 receptor A is homozygous. We don’t know exactly how it plays out, but if somebody has autoimmune disease for example, like Crohn’s disease, it could be related to to the genotype. Now, we have the iron and hemochromatosis section. The three most important genes related to iron overload are the HFE snips, these three here.
These first two are the ones that are most significant, or the bottom two I should say, HR63D and the C282Y. She’s minus minus, so that’s good. We don’t expect that. But again, that’s another one of those biomarkers. If she was homozygous or even compound heterozygous, plus minus for both of those two variants, that usually translates into higher ferritin levels. Ferritin is an intracellular storage form of iron. It’s used to assess iron deficiency, but also when it’s high, it can be really toxic. There’s been some associations in recent years over iron toxicity and chronic illness because when iron oxidizes, it forms free radicals, the hydroxyl free radical, which damages organs.
One of the complications that hemochromatosis causes is organ failure, organ damage, because of the iron toxicity. People that have that variant, they’ll need to phlebotomize more, give blood to lower the ferritin levels. But she’s minus minus, so we don’t expect that to necessarily be a problem. Now, here’s the methylation section and it’s all broken down into the different parts of the methylation cycle. The MATA1 variants are… This is the gene that makes the main methyl donor SAMe, SAMe, S-adenosyl-L-methionine. She’s heterozygous for a few of these snips. I don’t know if that’s necessarily significant. I usually don’t consider that to be a problem. Sometimes if a person is plus plus on a bunch of them, I’ll consider that to be significant.
That can play out with mood disorders and depression and OCD and anxiety disorders in some cases because all these different mental reactions, including the neurotransmitters, use the SAMe molecules as its methyl donor. We have some of the other sections here, so AHCY, BHMT, CDS, COMT. This is a minor allele that she’s got here. The major alleles for COMPT are 1508M and the H62H. COMT is the gene that’s… It methylates estrogen, but it also is metabolizing and breaking down, detoxifying the neurotransmitter dopamine. People that are plus plus, like myself for example, tend to have higher dopamine levels, and that can be good or bad depending upon how you interpret that information.
She’s minus minus, so we don’t automatically assume that her dopamine metabolism is an issue. Then we saw the GAD1 snips earlier when we looked at her brain health genetic section. Remember, this is a related to methylation. GAD1 has the B6 and B1 co-factors that it uses to make GABA. Then miscellaneous snips in the methylation section. G6PD, that one rarely shows up as positive. People that have a Mediterranean descent or Eastern European or Iraq, Iranian, in that region of the world, they may have plus plus inherited that. That can significantly affect the the redox process and the reduction of glutathione for example. It’s not an issue here. Some of these other variants are showing up, MTHFS and MTHFD1.
These are methylation genes related to folate metabolism. It could be something going on with the folate methylation looking at just kind of the overall picture of it, full R2, MTHFD1, and then there’s a few T2 that we looked at before. Some other steps related to methylation, just a bunch. MTRR is methylating B12. Heterozygous for one of these, but not really for all of them. We get to the mitochondrial genetic section. This is an interesting section. We look at the NDUFS7 gene. This is CoQ10 accepting electrons in the mitochondria. We know CoQ10 is really important for energy production, as well as to protect the mitochondria from free radical damage. Here’s our next section, the oxalate-related genes section.
This is a really, really interesting section, and I’m really excited to have added this recently. It turned out that in this client’s case, identifying oxalate problems was a huge, huge turning point for her health. Getting it really to go forward in a positive direction. Oxalates are a product of calcium metabolism, or I should say that they get metabolized in the gut from various foods that contain them. Spinach, Swiss chard, almonds, for example, have high oxalates. SPP1 is a gene known as osteopontin 1. It’s interesting because as we see, she’s homozygous here for four of these variants. Now, she came to me.
One of her main symptoms that she was experiencing was she would eat any kind of sulfur containing food and have reactions, headaches and fatigue and nausea, and things like this. I thought about that. That’s really curious I thought because oxalate competes with sulfur in the cells. I thought it was really interesting. She was avoiding eating protein foods, meat, poultry and eggs for example, because they all contain sulfur amino acids, but that wasn’t the problem. The problem was that she was having oxalate issues. As soon as she began to reduce her intake of oxalate foods, it was a huge turning point in her health.
It was this genetics report section that found these four variants that led to the identification along with the fact that she was having the sulfur intolerance. That was really the turning point for her. That’s how you use the genetic information. You can use the test as an initial point of contact saying based on your symptoms, this looks like it’s relevant. It turned out that it was. Eventually as she reduced the oxalate foods, she was able to tolerate sulfur again. Consequently, her heart rate variability, which is a measure of the autonomic nervous system, improved. Her HRV markedly increased and it basically stayed at that level even to this day.
These genes are potentially really relevant because they’re involved in the metabolism and the activities of oxalic acid. The other good thing about this is that we can track the excretion of oxalates, and oxalates can be excreted to the urine. You can look at an organic acids test to get an assessment of that. Oxalates can cause pain. When they bind to calcium, they form crystals. This is toxic to the mitochondria is it’s been shown. It also can cause myofascial pain, muscle pain, connected tissue pain, joint pain, and different kinds of complicating issues can arise as a result of hyperoxaluria. There’s all kinds of different protocols that can be created to break oxalates down to reduce their absorption.
When we start to get into this research, we started to see that there are some therapeutic opportunities. This section is really unique and interesting because it helps to shed light on the oxalate-related problems that somebody may have inherited. Next is the SHBG, sex hormone-binding globulin. This is a gene that produces a protein that the liver makes called SHBG. Again, another blood biomarker that we can monitor and track. The genotype risk factors are coded for people that have higher levels of SHBG, which I interpret to be a risk. SHBG will irreversibly bind sex hormones, estrogen and testosterone, and meaning that those hormones become inactive by the SHBG binding. What we know is that SHBG has an inverse relationship with insulin.
People on ketogenic diets may have lower insulin levels and that lower insulin raises their SHBG. We know in the diabetes research people with higher insulin levels have lower SHBG, so there’s an inverse relationship between insulin and SHBG. Now, if somebody has a genotype like this and is on a strict ketogenic diet, they may really need to pay attention to their SHBG. Not only because you need your sex hormones for the endocrine system obviously, but sex hormones play really important roles in other things the body is doing. Estrogen and testosterone are both what are called neurosteroids, so they have an effect on the brain and the mood and behavior. Both of them play important roles in immune cell signaling in the immune systems.
There’s a lot of different implications for elevated SHBG levels. The genotype can give you some insight into saying, “Hmm, maybe if I have this, I should look at my blood SHPG protein.” This is a section that looks at a few different snips related to the thyroid function and not really that much going on here.