COMT: Function & Health Implications of a Dopamine Gene

One mutation in the COMT gene may change the way we experience stress and pain. Are you a worrier or a warrior? Read on to find out. Catechol-O-Methyltransferase (COMT) is one of several enzymes that degrade dopamine , epinephrine, and norepinephrine . COMT breaks down dopamine mostly in the part of the brain responsible for higher cognitive and executive function (prefrontal cortex) [ 1 ]. Catechol-O-Methyltransferase is an enzyme that transfers methyl groups (hence the name methyltransferase). COMT introduces a methyl group to the catecholamine (dopamine, epinephrine, and norepinephrine), which is donated by S-adenosylmethionine ( SAM ). SAM is required for COMT to work properly [ 2 ]. Having too little SAM (s-adenosylmethionine) and too much SAH (s-adenosylhomocysteine) from undermethylation results in COMT inhibition as well [ 3 ]. A study of adolescent substance use (cigarette smoking, alcohol, and cannabis) found a complex association between COMT methylation and substance abuse [ 4 ]. One of the most researched variants in the human genome is a point mutation in the COMT gene called V158M (or rs4680). It has been associated with differences in intelligence, personality, and disease risk. The A allele results in 3 to 4-fold decrease in COMT enzyme activity [ 5 , 6 ]. This gene variant has been associated with differences in cognitive flexibility, impulse control, abstract thought, and being able to follow rules or task structure [ 1 ]. If you have AA then you will have the highest dopamine, while GG results in the lowest dopamine. AG is somewhere in the middle; the difference between AA and GG is studied more often than the difference between either homozygous genotype and AG. Meanwhile, very high and very low dopamine have each been associated with decreased cognitive performance [ 7 , 8 ]. Under stress, dopamine increases. […]

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