Insights into the body’s detox ability may be determined by uploading DNA raw data from genetic testing companies like 23andMe to identify the GST gene variant carried. The GST genes are responsible for synthesizing and recycling glutathione.
The glutathione/GST system is one of the body’s most important detox mechanism, which lowers oxidative stress and plays an important role in DNA repair, immunity and detoxification of chemicals, metals and estrogens.
The enzymes that belong to the family of glutathione S-transferase (GST) and cytochrome P450 (CYP) families are associated with a two-stage detoxification process for multiple toxins and potential carcinogens. Phase I enzymes act on most potentially toxic compounds and then these activated metabolites undergo detoxification by phase II enzymes, especially GST.
There are eight classes of the GST enzyme, from alpha to zeta (names GSTA, GSTM etc). These enzymes detoxify toxins by adding a glutathione and are found mainly in the liver but are also found in other parts of the body like the intestine. [/vc_column_text][vc_separator color=”white” el_width=”50″][vc_single_image image=”34148″ img_size=”large” add_caption=”yes” alignment=”center”][vc_separator color=”white” el_width=”50″][vc_column_text]
Any toxin that has been conjugated with glutathione by the GST enzyme is then removed from the body in the urine or in the bile.
Research studies have shown that phase I and phase II gene polymorphisms are associated with the risk for the following diseases
Here are a few common polymorphisms in the GST gene that are associated with the level of glutathione transferase activity. To find out the inherited variant of GSTM1 23andme DNA raw data is all that is required. There are extensive pubmed entries for GST polymorphism and their associated disease risk.
Check your 23andMe raw data or Ancestry DNA raw data to identify which variant of rs366631 you carry.
| Genotype | Phenotype |
|---|---|
| AA | More likely to have lower enzyme activity |
| GA | More likely to have normal enzyme activity |
| GG | More likely to have normal enzyme activity |
Check your 23andme raw data or ancestry DNA raw data to identify which variant of rs3957357 you carry.
| Genotype | Phenotype |
|---|---|
| AA | More likely to have lower enzyme activity |
| GA | More likely to have normal enzyme activity |
| GG | More likely to have normal enzyme activity |
Check your 23andme raw data or ancestry DNA raw data to identify which variant of rs1695 you carry
| Genotype | Phenotype |
|---|---|
| AA | More likely to have normal enzyme activity |
| GA | More likely to have reduced enzyme activity |
| GG | More likely to have reduced enzyme activity |
There are genetic testing services like Genetic Genie detox profile which lists even GSTT1 null alleles that are present in the 23andme raw data. However, the genetic genie detox profile interpretation does not include recommendations that Xcode Detox profile does.
References:
23andme celiac disease genetic testing involves assessment of genetic markers associated with gluten sensitivity and celiac disease from your 23andme raw data. The DNA raw data is available to you when you buy the 23andme genetic test for Ancestry.
In recent years, the number of people found to have celiac disease has grown many folds due to increased awareness and ease of diagnosis.
So, why do you need to do genetic testing for coeliac disease? About 1 in 100 people in the U.S have celiac disease. However, 2.5 million people with celiac disease do not know that they have it, i.e they are undiagnosed.
Here are a few important facts about celiac disease genetic testing that everyone must know.
| Celiac Disease | Gluten Intolerance |
|---|---|
| Rare condition. Only 1% of the population is known to be affected with this condition. | Compared to celiac disease, gluten intolerance is more prevalent. |
| This is an autoimmune condition and it involves the immune system. | This is not an autoimmune condition and it does not involve the immune system. Symptoms of gluten intolerance or gluten sensitivity are restricted to abdominal discomfort |
| The only treatment is to completely avoid gluten in the diet | The amount of gluten consumed should be below the body's threshold level. |
| This is a more severe condition | This is less severe when compared with celiac disease |
| Genotype HLA DQ 2.5 (rs2187668) | Phenotype |
|---|---|
| CC | [Advantage] More likely to be gluten tolerant |
| CT | Moderate risk for gluten intolerance |
| TT | [Limitation] More likely to be gluten intolerant |
| Genotype | Phenotype |
|---|---|
| AA | [Advantage] More likely to be gluten tolerant |
| AG | Moderate risk for gluten intolerance |
| GG | [Limitation] More likely to be gluten intolerant |
| Genotype | Phenotype |
|---|---|
| rs2395182- T | [Limitation] More likely to be gluten intolerant |
| rs7775228- G | [Limitation] More likely to be gluten intolerant |
| rs4713586-A | [Limitation] More likely to be gluten intolerant |
| Genotype | Phenotype |
|---|---|
| GG | [Advantage] More likely to be gluten tolerant |
| AG | Moderate risk for gluten intolerance |
| AA | [Limitation] More likely to be gluten intolerant |
References:
Vitamin A is important for good vision, healthy eyes, healthy skin, and to fight infections.
Yet, it cannot be synthesized by the body.
Therefore, it becomes an essential nutrient that needs to be included in the diet.
Conversion of beta carotene to vitamin A is an important metabolic pathway which is genetically influenced.
Vitamin A refers to the interconvertible compounds retinal and retinol.
Both these can be converted into various other metabolites that are functionally important.
The transformation into these metabolites is irreversible.
Retinoic acid is one such metabolite.
Foods like milk, liver, fish oil, and eggs contain preformed vitamin A.
Beta carotene found in carrots and green leafy vegetables can be converted in the body into vitamin A, an important source for vegetarians.
Beta carotene is an ideal provitamin A carotenoid, and it needs to be converted into active vitamin A in the body.
Carotenoids are found in plants, and they are responsible for the distinct colors that some fruits and vegetables boast of.
Carrots get their orange color because of beta carotene.
According to the National Institute of Health, the following are the recommended units for the daily intake of beta carotene:
Once it is consumed, beta carotene is converted into vitamin A, which is then utilized by the body for various functions.
It is estimated that nearly 50% of vitamin A in a diet is due to beta carotene and other such carotenoids.
The major organs that are associated with beta carotene conversion are the liver and the intestines.
The liver is associated with storing significant proportion of retinoid.
There are two enzymes associated with beta carotene conversion to vitamin A, including:
Converting beta carotene to vitamin A is extremely variable with the estimated number of low responders to dietary beta carotene as high as 45%.
Genetic variants in the BCMO1 gene are associated with the conversion of beta carotene into retinol.
Check your Ancestry DNA or 23andMe raw data results for SNP rs7501331 that you carry
| Genotype | Phenotype |
|---|---|
| TT | [Limitation] Likely reduced beta carotene conversion |
| CT | [Limitation] Likely reduced beta carotene conversion |
| CC | [Advantage] Likely normal beta carotene conversion |
Check your Ancestry DNA or 23andMe raw data results for SNP rs12934922 that you variants
| Genotype | Phenotype |
|---|---|
| TT | [Limitation] Likely reduced beta carotene conversion |
| AT | [Limitation] Likely reduced beta carotene conversion |
| AA | [Advantage] Likely normal beta carotene conversion |
Enzyme activity based on genetic variant carried
A study by researchers from Newcastle University showed that individuals who carry the T allele of rs7501331 have a 32% reduction in enzyme activity while individuals who carried T allele for both rs7501331 and rs12934922 had a 69% reduction in enzyme activity.
A more recent study by researchers from the same university showed that apart from these two genetic variants in the BCM01 gene, there were other variants that had an influence on enzyme activity.
Other variants of interest are rs11645428, rs6420424, and rs6564851.
Vitamin A is important for vision and is used in the treatment of cataracts and age-related macular degeneration.
It is also important for the skin and immune system.
Vitamin A deficiency is major public health across the world. Each year, approximately 250,000–300,000 vitamin A-deficient children become, and half of them have been reported to die within a year after getting blind.
The following are some of the symptoms of vitamin A deficiency:
Hand-picked content for you: Genes can Influence your Vitamin A requirement- Here’s how
Beta carotene is considered pre-vitamin, but it also is known to have certain benefits.
Each carrot is known to contain about 10 – 50 mg of beta carotene, apart from other nutrients.
The following are some of the foods rich in beta carotene
| Range mg/100 g | β-Carotene |
|---|---|
| 20 -50 | Red peppers, carrot and paprika |
| 10 -20 | Carrots, red peppers |
| 5 to 10 | Acai berry drink, carrot juice, carrots, chili powder, kale, parsley pumpkin, spinach, turnip greens |
| 1 to 5 | Apricots, broccoli, cabbage Chinese, cherries, chicory greens endive, lettuce (green and red leaf), melons, oregano, parsley peas green, peppers green, plums, pumpkin, sweet potato, thyme, watercress |
Excess of retinoids is known to lead to teratogenic effects.
High levels of beta carotene are known to increase the risk for certain types of cancers.
One study found that there was an increased risk of lung cancer after β-carotene supplementation among smokers and people who drank more than 11 g ethanol/d.
High levels of beta carotene can affect the skin and lead to a condition known as carotenodermia.
The soles of the feet and the palms turn yellow.
Too little beta carotene or too much both have their share of risk, which makes genetic testing for vitamin A needs important.
How well your body converts beta carotene into retinol or vitamin A will help you identify the amount of beta carotene that should be consumed, from the diet or as a supplement.
Upload your 23andme raw data or any other ancestry raw data to avail Xcode Life’s Gene Nutrition Report can be used to identify your vitamin A needs.
| CHIP Version | Vitamin A SNPs |
| 23andMe (Use your 23andme raw data to know your DRD2 Variant) | |
| v1 23andme | Present |
| v2 23andme | Present |
| v3 23andme | Present |
| v4 23andme | Present |
| V5 23andme (current chip) | Present |
| AncestryDNA (Use your ancestry DNA raw data to know your DRD2 Variant) | |
| v1 ancestry DNA | Present |
| V2 ancestry DNA (current chip) | Present |
| Family Tree DNA (Use your FTDNA raw data to know your DRD2 Variant) | |
| OmniExpress microarray chip | Present |
Updated 21st June, 2021
The COMT gene codes for the production of catechol – O -Methyltransferase enzyme. This enzyme is associated with degrading neurotransmitters, transfering methyl groups to epinephrine, norepinephrine and dopamine ( catecholamines).
By uploading DNA raw data from 23andme COMT gene variant carried may be determined ,which can also be used to identify tendency for specific personality traits.
The COMT enzyme is also associated with the breakdown of certain drugs prescribed for hypertension, Parkinson’s disease and asthma.
The following processes are associated with the COMT variant under study.
Catechol estrogens- role in cancer
The catechol estrogens are associated with hormone regulation and can have a potent endocrine effect. The hormones that may be affected by these catechol estrogens include prolactin, luteinizing hormone and follicle stimulating hormone.
Estrogens are known to lead to cancer by encouraging proliferation of cells and resulting in damage. These hormones are found to be highly mitogenic, especially in sensitive tissues like breast and uterus. When such sensitive tissues are exposed to such mitogenic stimulation for a prolonged period of time, it is found to lead to cancer.
Estradiols are found to cause DNA damage (sister chromatid exchange and chromosomal aberrations). Such genotoxic effects are also produced by catechol estrogens
Mechanism of conversion to Catechol estrogens:
In the liver, CYP3A4 oxidises estrone and estradiol to 2-hydroxycatechols and by CYP1A in extrahepatic tissues. In extrahepatic sites, CYP1B1 oxidises estrone and estradiol to 4-hydroxycatechols.
The concentration of 4-hydroxyestradiol is found to be the highest in cancerous tissues when compared with the different types of estrogens. In the hypothalamus and in the pituitary glands, the concentration of catechol estrogens is found to be 10 times more than the parent estrogens.
Studies have also shown that catechol estrogens have a more carcinogenic effect on mice than estradiol. These catechol estradiols compete with estradiol for binding to
23andme COMT Variant in lowering Cancer risk:
The Catechol estrogens that are known to affect DNA and result in cancer or autoimmune conditions are converted into methoxy estrogens.
2- and 4-o-methylethers, products of COMT, are excreted in the urine and are found to be less harmful.
Using the DNA raw data of 23andme COMT gene variant carried by an individual can be used to identify the level of inhibition of COMT. Increased inhibition could lead to increased levels of catechol estrogens.
The reactive oxygen species produced by the catechol estrogens not only increases risk of cancer but also for other autoimmune conditions like rheumatoid arthritis and systemic lupus erythematosus.
This variant of the COMT gene is well studied and is associated with warrior/ worrier personality (personality), pain tolerance(fitness) and in cocaine dependence (Substance dependence) and disease risk (Health)
rs4680- The wild type allele codes for valine while the A allele codes for methionine. This change in amino acid results in nearly 25% reduction in enzyme activity. This results in increased dopamine among A allele carriers.
Upload your 23andme raw data or your Ancestry DNA raw data to find the variant of rs4680 that you carry
| Genotype | Phenotype |
|---|---|
| GG | More likely to have higher enzyme activity and lower dopamine level |
| GA | Moderate enzyme activity and moderate dopamine level |
| AA | More likely to have lower enzyme activity and higher dopamine level |
COMT gene and personality
A study conducted to identify the effect of this COMT variant showed that Valine carriers have better prefrontal hyperactivation and were better at responding to adverse stimuli. These individuals was classified by the researchers as having warrior personality. The met allele carriers had better memory and an advantage in attention tasks. These individuals were termed worriers by the researchers, providing a way to identify warrior and worrier personalities.
By uploading Raw data from 23andme COMT variant carried can be used to identify certain other personality traits as well- A study conducted in 2015 on normal adults showed that people who carried specific variant of this COMT gene scored lower on neuroticism while they had higher scores for conscientiousness and agreeableness.
Xcode Personality report provides information on genetic tendency for certain personality traits, including warrior and worrier personality, and the big 5 personality traits.
COMT gene and Disease risk
COMT variant is important in identifying the risk for schizophrenia. A study conducted in 2016 showed that the COMT gene variant was associated with negative symptoms of schizophrenia and bipolar disorder.
Xcode health report includes susceptibility for more than 45 diseases, including schizophrenia.
COMT gene and Cocaine dependence
The COMT variant is known to influence prefrontal cortex (PFC) dopamine regulation which has been associated with cognition and personality. However, PFC dysfunction is also important in cocaine dependence, which could contribute to loss of control and, thereby, dependence. This variant has also been implicated for other substance abuse.
Xcode Substance dependency report includes risk of dependency for many substances including cocaine, cannabis, heroin, alcohol and nicotine.
COMT gene and Pain
In a study conducted by researchers from The University of Michigan, COMT variant was associated with the intensity of pain.
Effect of gender on COMT gene variant
The activity of COMT enzyme is about 305 lower among females as it is decreased by the presence of estrogen. This results in greater dopamine activity in females than in males. Therefore men benefit from increasing their dopamine levels than females.
Studying DNA raw data from 23andme will help in identifying individuals who have low COMT enzyme activity and who have higher levels of dopamine, which can eventually build up . However, consumption of certain methyl donor supplements can result in a fall in dopamine levels that can lead to mood swings.
Some supplements include
COMT and MTHFR
The COMT enzyme plays a role in methylation. Individuals who carry genetic variants associated with lower MTHFR enzyme and genetic variants associated with lower COMT enzyme will be more prone to the effects of stress.
DNA raw data from 23andme and other genetic testing services can be used to identify varied risks and benefit based on the COMT variant carried by an individual. Select from the list of Xcode reports available to help tailor lifestyle based on the genetic variant carried.
References:
23andme Hemochromatosis status can be used to identify a hereditary condition in which the body absorbs the excess of iron from the food consumed. Iron is important for various functions like oxygen transport and for oxidative phosphorylation. While iron deficiency can lead to anemia, excessive iron can lead to iron-overload. The iron levels in the body can be determined by evaluating serum iron levels, serum transferrin and saturation of transferrin with iron. It has been estimated that 25 to 50% variation in these blood iron markers is due to genetic variants carried by an individual.
Normally about 8 to 10% of iron from food is absorbed in the body, however, in people with hemochromatosis, there is 4 times increase in absorption. This condition of iron overload is also known as genetic hemochromatosis and leads to the slow accumulation of iron which can eventually lead to organ damage. DNA raw data can be used to check for variants in the hemochromatosis gene, C282Y and H36D.
Evolutionary origin of hemochromatosis gene mutation:
Genetic variants to specific traits are inherited due to an environmental pressure that either triggered the mutation or which encouraged people with the variants to survive. Evolutionary biologists believe that this condition arose as a result of low iron reserves from food in the Celtic region, about 6000 years ago, which necessitated storage of available iron from food. Though this variant was beneficial during the period of poor iron reserves and when the risk of maternal iron deficiency was high, this condition can lead to serious health effects now, if left undetected.
What are hereditary hemochromatosis symptoms?
Hereditary hemochromatosis is present from birth, as it is caused due to the presence of a genetic variant. However, most people with this condition exhibit symptoms only during middle age. Men are more likely to show symptoms at an earlier age, in their 30s. Women begin to show symptoms only postmenopause, when they no longer lose iron during their monthly menstruation or during pregnancy.
The symptoms are usually mild or remain undetected as most of the symptoms are similar to common conditions. Hereditary hemochromatosis symptoms include
How do hemochromatosis gene variants lead to iron overload?
The liver secretes a hormone called hepcidin which is responsible for maintaining iron levels in the body, how much is absorbed and where it is stored. Certain genetic variants in the hemochromatosis gene disrupt the functioning of hepcidin and result in excessive absorption of iron from the food consumed. This excess iron is then stored in the liver and other major organs. Over a prolonged period of time, the excess of iron in such organs can lead to organ failure, diabetes or heart failure.
How do you find out your 23andme hemochromatosis status?
Upload your DNA raw data from 23andme to find out your hemochromatosis status. There are essentially two significant genetic variants in the HFE gene associated with hemochromatosis.
Significant of the two is C282Y, people who carry two AA are associated with a higher risk for hemochromatosis. According to a study published in the American Journal of Human Genetics, the C282Y variant contributes to 26% variation in ferritin levels among monozygotic twins and 20% phenotypic variation.
Using DNA raw data to find your hemochromatosis status
Upload your 23andme or your Ancestry DNA raw data to find which variants of rs1800562 you carry
| Genotype | Phenotype |
|---|---|
| AA | [Limitation] Likely higher risk for hemochromatosis |
| AG | [Limitation] Likely moderate risk for hemochromatosis |
| GG | [Advantage] Likely normal |
Upload your 23andme or your Ancestry DNA raw data to find which variants of rs1799945 you carry
| Genotype | Phenotype |
|---|---|
| GG | [Limitation] Likely higher risk for mild hemochromatosis |
| CG | [Limitation] Likely moderate risk for mild hemochromatosis |
| CC | [Advantage] Likely normal |
Who is a hemochromatosis carrier?
A person who has one risk variant of rs1800562 and one normal variant is considered to be a carrier. Approximately 1 in 10 Americans carry one copy of this variant and are carriers.
Compound heterozygous: People who carry one risk variant of rs1800562 and one risk variant on rs1799945 have a higher risk of developing hemochromatosis if the variants are on separate chromosomes, one from the father and the other from the mother.
What are the different types of hemochromatosis?
Apart from hereditary hemochromatosis, there are other hemochromatosis conditions that can lead to iron overload.
Will everyone with the hemochromatosis HFE C282Y variant develop iron overload?
Nearly 1 in 200 Americans carry two copies of the A variant of C282Y, which increases their risk for hemochromatosis. Not everyone who carries two copies of this variant develops hemochromatosis, only about 10 % develops iron overload. Early identification of the genetic variant carried will help in managing this condition and help prevent tissue damage due to excess iron.
How will knowing more about your 23andme hemochromatosis status help?
Identifying the genetic variant carried will help in altering lifestyle and dietary habits to prevent excess iron in the body, specifically in organs and tissues.
The following are some important ways to manage hemochromatosis
Upload your 23andme raw data or your Ancestry DNA raw data to find out your hemochromatosis status by availing Xcode health report here.
References
Genetic variants in MTHFR and vaccines induced reactions have been discussed since the publication of the study titled “Genetic basis for adverse events after smallpox vaccination”, conducted by the Dartmouth Public School. The study was carried out to identify the basis for adverse reactions among certain individuals to vaccines.
There were two independent studies that were detailed in the study about MTHFR and vaccinations. It was found that study subjects who were vaccinia-naïve subjects developed pock formation at the site of vaccination. A section of the study subjects also developed fever, lymphadenopathy or even rash, prompting the researchers to find out if genetic polymorphisms made them more susceptible to such systemic effects.
A single nucleotide polymorphism in MTHFR gene (rs1801133) has been associated with adverse reactions to vaccines, in the study involving small pox virus. This polymorphism leads to a change in amino acid from alanine to valine, affecting both the quality and the quantity of the MTHFR enzyme.
Top 3 Functions of MTHFR enzyme:
Effects of MTHFR Gene Mutations:
MTHFR genetic variation is associated with
The study details that an increase in homocysteine levels, associated with a certain genetic variant of MTHFR, could stimulate an inflammatory response. According to the study, this could lead to the adverse reaction due to the effect of MTHFR and vaccine injection.
An alternate pathway to explain MTHFR gene mutation and vaccines induced side effects is that the rapid proliferation of cells caused by vaccination can increase the need for DNA synthesis. Genetic polymorphism in the MTHFR gene, and thereby the activity of the MTHFR enzyme, may be significantly associated with this process. The study also noted that genetic variation in MTHFR and vaccines induced cardiac events should be evaluated in future research studies.
Though there does not seem to be considerable research associated with MTHFR mutation and vaccines, there is a lot of speculation about the safety of vaccination. This genetic variant in the gene MTHFR has prompted many groups to advocate against vaccination for children. However, we have not found sufficient scientific evidence to support this notion.
Insufficient evidence for MTHFR kids vaccination induced injury
Vaccine injury is one of the major topics of debate and, in the United States, there is an exemption from liability for drug manufacturers as well as for the physician. Though there are severe instances of vaccine injury, which includes permanent disability, an autoimmune condition or even death.
While there is under-reporting of vaccine injury, with symptoms showing up even after a few weeks, there have been very few gene based studies of significance.
Apart from the C677T variant in MTHFR, vaccines induced adverse effects were also found, in the study, to be significantly associated with genetic variants in the following genes
Since smallpox has been eradicated from most parts of the world, the relevance of this study and the genetic basis of MTHFR vaccine injury is questionable.
Apart from this study on small pox vaccine, another study was conducted on MTHFR MMR vaccine. This study conducted in 2014 was aimed at identifying genetic variants among children with MMR associated fever. There are 5 genes which were found to be associated with vaccine injury
Mercury is known to be a potent neurotoxin, however, a study conducted in 2014 showed a potential genetic basis. The study showed an initial association between A1298C (rs1801131) variant of MTHFR and vaccine injury. Another variant associated with variance in response to mercury was identified in PON1 (rs662). However, none of the vaccines currently in use include mercury.
Let’s look at the incidence of occurrence of serious adverse effects of vaccines.
Compare that with the number of people who are homozygous for C677T, the variant under study
Since 40% of the U.S population carries at least one copy of C677T polymorphism, and comparatively, very few people develop adverse effects, testing for MTHFR-vaccine effect is not appropriate, till further validation studies confirm the need for such screening.
Upload your raw data to find your MTHFR variant
MTHFR variants play an important role in the amount of folic acid supplementation required, as well as in the need for detoxification.
MTHFR and detox:
Some people are more susceptible to mold exposure or may require a longer period of detoxification to help their liver recover from all the pollutant exposure, but how do you find out who does? Upload your 23andme raw data or your ancestry DNA raw data to identify the variant present in your genes.
Though this information may not aid in understanding MTHFR and vaccine adverse effect correlation, it will help in identifying the variant carried and steps to align your lifestyle for better health.
References:
