What are COMT gene mutations?
COMT (catechol-O-methyltransferase) helps break down certain neurotransmitters and catecholamines. These include dopamine, epinephrine, and norepinephrine. Catechol-O-methyltransferase is important to the areas of the pre-frontal cortex. This area of the brain is involved with personality, inhibition of behaviors, short-term memory, and planning. While abstract thinking, and emotion. COMT is also involved with metabolizing estrogens. COMT catalyzes the transfer of the methyl-group from SAM to catecholamine substrates. Like L-DOPA, dopamine, epinephrine and norepinephrine.
COMT individuals can usually break down these neurotransmitters efficiently. But some COMT individuals may have trouble breaking these chemicals down from impaired function of the enzyme. With a positive COMT status, it has been clinically observed by physicians. Those people may have trouble with methyl donors. This can lead to irritability, hyperactivity, or abnormal behavior. They may also be more sensitive to pain. COMT mutations slow the activity of the COMT enzyme which slows dopamine causing dopamine excess of imbalances.
COMT is also important in the detoxification of xenobiotics and metabolism of catechol drugs. COMTV158 is associated with a 3-4 x reduction or increase in activity and increased reaction to heat.
COMT V158M + H62H heterozygous is associated with low or high catecholamines.
V158M + H62H homozygous is associated with high catecholamines and excess estrogen.
COMT problems / Symptoms
Possible estrogen imbalances and or estrogen dominance:
- Social anxiety
- Bipolar disorder
- Thyroid abnormalities
- Poor libido
- Poor memory
- Hot flushes
- Hormone imbalances
- Development disorders
- Neurological disorders
- Menopausal symptoms
- Andropausal symptoms
Reduced tolerance for methyl donors such as:
- Methyl B12
- SAMe (S-Adenosyl methionine)
- MSM (Methylsulfonylmethane)
- DMG (Dimethylglycine)
- TMG (Trimethylglycine) or Betaine
- Green powders/smoothies
Dopamine disruption from COMT
Because COMT can interfere with dopamine this causes imbalances such as high dopamine or low dopamine.
- Driven to create situations that stimulate them mentally and physically
- This may lead to violent, destructive or illegal behavior if left unchecked
- Dr’s use antipsychotic medications to reduce a patient’s dopamine levels
- Addictive tendencies
- Tremors / restless legs
- Low libido
- Lack motivation
- Mental exhaustion
- Dull, boring dreams
- Risk of developing alcohol abuse or dependence
Problems with COMTV158
- Associated with violent behavior
- Significantly associated with schizophrenia
- Increased susceptibility to psychosis
- Better performance tests of prefrontal cortex function and working memory
- Means increased tyrosine hydroxylase expression and increased dopamine levels
- COMT V158 – more susceptible to pain
- Affects cognitive function
COMT & allele gene variants
Alleles (An allele is a variant form of a gene).
rs4680(A) = Worrier. Met, more exploratory, lower COMT enzymatic activity, therefore higher dopamine levels, and lower pain. Threshold, enhanced vulnerability to stress, yet also more efficient at processing information under most conditions.
rs4680(G) = Warrior. Val, less exploratory, higher COMT enzymatic activity, therefore lower dopamine levels and higher pain threshold. But better stress resiliency, albeit with a modest reduction in executive cognition performance under most conditions.
(AA allele) = Low activity or higher dopamine which needs certain nutrients for support B6, SAM, magnesium, and FAD.
(G allele) = High activity or lower dopamine which need inhibitors such as quercetin, green tea, and Rhodiola.
Vitamin D & COMT
Vitamin D has previously been shown to influence midbrain dopaminergic neuron function. While increasing the rate-limiting synthetic enzyme for dopamine.
COMT Liver detox – Phase 2
- COMT/TXNRD2 A4251G
- TXNRD2 T2439C
COMT Neurotransmitter Pathway: Serotonin & Dopamine
- COMT61 P199P
- COMT61 P199P
- COMT V158M
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