The COMT Gene and Its Mutations
Catechol-O-methyltransferase, or the COMT gene, is located on the q arm of chromosome 22 and provides instructions for producing an enzyme called catechol-O-methyltransferase.
This enzyme deactivates neurotransmitters (chemicals in the brain) like dopamine, epinephrine, and norepinephrine.
There are two versions of the enzyme made by the COMT gene:
- The longer form of the enzyme called membrane-bound catechol-O-methyltransferase (MB-COMT) is produced by the nerve cells in the brain.
- The shorter form of the enzyme called soluble catechol-O-methyltransferase (S-COMT) is produced by other tissues like the liver, kidneys, or blood. This form of the enzyme helps control levels of some hormones.
The COMT gene deactivates these neurotransmitters in their normal form by adding a methyl group to their structure.
When there are abnormal changes (mutations) in the COMT gene, it cannot function normally, and the body struggles to eliminate toxins and harmful chemicals.
Understanding the COMT Gene
The COMT Warrior and Worrier Genotypes
Find Out Your COMT Gene Type With The Personality Report
Studies have shown that single nucleotide polymorphisms (SNPs) in the COMT gene affect its activity, resulting in ‘warrior’ and ‘worrier’ traits.
The most common variant in the COMT gene was found to be the substitution of methionine (Met) in the place of valine (Val) at position 158.
Based on the number of variant gene copies, an individual is classified as:
- Worrier (A genotype)
- Warrior (G genotype)
- A mix of the two (AG genotype)
The Warrior
Individuals having two copies of the G allele have a higher COMT enzyme, which means lower dopamine levels in the brain.
They also have a higher pain threshold and greater capacity to deal with stress at the expense of cognitive performance.
For this reason, people with GG genotype are termed as Warriors.
The Worrier
The COMT enzyme formed from the A allele has a 75% reduction in activity compared with the one formed from the G allele.
So, people with the AA genotype have lower COMT enzyme activity and increased dopamine levels in the brain.
They have a lower pain threshold and increased sensitivity to stress, earning them the name ‘Worriers.’
These individuals also show improved memory and attention to detail but with a greater risk for Parkinson's disease.
Symptoms of COMT Gene Mutation
The symptoms of COMT gene variation differ in people. Some common symptoms observed in people with COMT gene mutation include:
- Estrogen imbalance
COMT gene mutations may cause estrogen imbalance, resulting in a wide range of symptoms such as:
- Fatigue
- Thyroid disorders
- Psychological issues like anxiety, bipolar disorder and depression
- Hormonal imbalances such as low libido or infertility
- Brain fog
- Increased allergies
- Early menopause
- Breast tenderness
- Neurological disorders
- Increased risk of cancers
- Dopamine imbalance
COMT gene mutation may cause an increase or decrease in dopamine levels. While high dopamine levels result in violent behavior, impulsivity, and schizophrenic tendency, low levels of the hormone may cause:
- Low libido
- Depression
- Tremors
- Mental and physical fatigue
- Addiction tendency
- Poor detoxification
The abnormal change in the COMT gene results in defective functioning of the enzyme, resulting in poor detoxification and elimination of toxins.
COMT Gene Mutation and MTHFR
The COMT gene mutation is closely associated with the MTHFR gene, and both are linked to Adrenal Fatigue Syndrome.
A mutation in the MTHFR or the methylenetetrahydrofolate reductase gene is common and is present as two main variations:
- C677T
- A1298C
Since you can inherit the COMT or the MTHFR gene mutations simultaneously, you should always test for both mutations, if required.
COMT and MTHFR genes are related to methylation, and the MTHFR gene affects how the COMT gene functions.
When the MTHFR gene activity is low, it lowers the activity of the COMT gene. The reduced activity of both these genes may have serious health consequences.
For example, the problem of poor detoxification is aggravated in people with a mutation in the MTHFR gene along with that in the COMT gene.
Tackling the COMT Gene Mutation
Image: Recommendations for COMT gene mutation
The COMT gene supports the detoxification process, and having a gene mutation affects it.
Since we cannot change genetics, here are some lifestyle changes to manage the COMT gene mutation in people who have it:
- Supplements to take
Since the COMT gene participates in methylation, here are some supplements that will support this function in people with the gene mutation:
- B vitamins
- Magnesium
- S-Adenosyl methionine
- Fluvic acid
- Marine phytonutrients
- Phytonutrients to eat and avoid
While phytonutrients are nutritious chemicals found in plants, you should ensure a good balance between the ones you consume and avoid.
Include more flavones, myricetin, and genistein that can be found in foods like onions, parsley, celery, grapefruit, and chamomile.
- Exercise everyday
Exercise is an effective stress buster and also ensures good overall health. Regular exercising increases methylation and catechol levels in the blood.
Discuss with your doctor the amount of exercise you require based on your COMT gene mutation.
- Avoid catechols and catechol estrogens
In people with a COMT mutation, their body finds it challenging to remove catechols.
So, it is best to avoid foods that increase catechol levels, and these include:
- Caffeine
- Alcohol
- Smoking
- High-protein foods
Excess estrogens in the body slow the COMT enzyme’s detoxification process, leading to a build-up of toxins and harmful substances.
So, you must avoid foods that increase estrogen levels in the body, including:
- Dairy
- Soya bean
- Parabens
Increasing your intake of foods like cauliflower, cabbage, broccoli, and flaxseeds helps detoxify the liver.
- Have regular meal times
When you go long without eating, the catechol level in the body increases. Regular mealtimes maintain steady blood sugar and catechol levels within the normal range.
- Practice effective stress reduction
People with the gene mutation tend to be more stressed, and its effects may be long-lasting. So, it is important to practice stress reduction through yoga, meditation, mindfulness, regular workouts, pursuing hobbies, and spending time with your loved ones.
- Support your liver
Your liver plays an essential role in the detoxification process in the body. So, if you have a COMT gene mutation, it is important to keep your liver healthy.
Some foods that help your liver in its detox process are:
- Cruciferous veggies like cauliflower, Brussel sprouts, broccoli
- Citrus fruits
- Teas like honeybush and rooibos
- Turmeric
- Antioxidant-rich fruits like strawberries, cherries, blueberries, and blackberries that contain Ellagic acid
- Herbs like rosemary
- Foods that contain ferulic acid (wheat, rice, oat, pineapples, nuts, and beans)
Summary
- The COMT gene is located on chromosome 22 and provides instructions for an enzyme that inactivates neurotransmitters like dopamine in the brain.
- COMT gene works by adding a methyl group to neurotransmitters and deactivating them.
- Mutations in the COMT gene give rise to two variants – warriors and worriers.
- People with GG genotype in the COMT gene have greater pain threshold and lower sensitivity to stress and are, therefore, termed warriors.
- People with the AA genotype in the COMT gene have lower pain thresholds and are more sensitive to stress, earning themselves the tag of worriers.
- Common symptoms of COMT gene mutation include estrogen and dopamine imbalance and their effects and poor detoxification.
- The COMT and MTHFR genes are related to methylation, and the latter affects how the COMT gene works.
- When the MTHFR gene activity is low, it automatically slows down the activity of the COMT gene.
- If you have the COMT gene mutation, taking supplements to boost your detoxification and protect the liver is recommended.
- Regular workouts, avoiding estrogen catechols, and some phytonutrients support healthy metabolism and detoxification in the liver.
References
https://medlineplus.gov/genetics/gene/comt/
https://www.mygenefood.com/genes/brain-and-mental-health-genes/comt/
