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.
Function of Comt Gene variant
The following processes are associated with the COMT variant under study.
- Epinephrine to Metanephrine
- Dopamine to 3-Methoxytyramine
- Norepinephrine to Normetanephrine
- Dihydroxyphenylethylene glycol (DOPEG) to Methoxyhydroxyphenylglycol (MOPEG)
- 3,4-Dihydroxymandelic acid (DOMA) to Vanillylmandelic acid (VMA)
- Methylation of catechol estrogens to methoxy estrogens- This is associated with reduction in risk of DNA damage and an elevation in concentration of 2-methoxyestradiol (2-MeOE2), which has an antiproliferative property.
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
- estrogen receptors in the hypothalamus and anterior pituitary gland
- dopamine receptors in anterior pituitary membranes
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.
COMT rs4680 (Val158Met)
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.
COMT gene variant and supplements
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
- methyl B12
- Curcumin
- catechol-containing flavonoids: quercetin, ferulic acid, rutin, fisetin and luteolin.
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:
- https://en.wikipedia.org/wiki/Catechol_estrogen
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583214/
- https://www.ncbi.nlm.nih.gov/pubmed/12595695
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