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COMT

From SNPedia

is agene
is mentioned by
Full namecatechol-O-methyltransferase
EntrezGene1312
PheGenI1312
VariationViewer1312
ClinVarCOMT
dbSNP1312
SADR1312
HugeNav1312
wikipediaCOMT
googleCOMT
gopubmedCOMT
EVSCOMT
HEFalMpCOMT
23andMeCOMT
UniProtP21964
EnsemblENSG00000093010
OMIM116790
EVSCOMT
# SNPs27
 Max MagnitudeChromosome positionSummary
Rs1655991.519,969,258
Rs16565619,961,340
Rs165688019,963,748
Rs16572219,961,490
Rs16577419,965,038
Rs1784930819,963,748
Rs202091719,941,361
Rs207550719,940,569
Rs209760319,940,569
Rs223939319,962,905
Rs308786919,953,984
Rs4633219,962,712
Rs464631219,960,814
Rs464631619,964,609
Rs46802.519,963,748warrior vs worrier; number of other associations
Rs481819,963,684
Rs599388219,950,010
Rs6267019,962,740
Rs626919,962,429
Rs73786519,942,598
Rs73786619,942,586
Rs740602019,962,745
Rs74060319,957,654
Rs769224019,964,281
Rs8192488019,963,714
Rs9332377019,968,169
Rs93327119,943,884

Variations in this gene control dopamine levels. This can be used to pick appropriate dosages of ADHD medications [1].

COMT met158 allele associated with OCD in men [PMID 17264842]

While the Val158Met allele (rs4680) has been well-studied and appears to affect brain function, there is evidence that COMT activity levels are largely controlled by a less-obvious mechanism. [PMID 15537663] studied rs6269, rs4633, rs4818, and rs4680, and grouped COMT function into three haploblocks based on pain response, which covered about 96% of the people tested:

-people in the GCGG block showed the lowest pain response, attributed to high COMT function

-ATCA people had intermediate pain response

-ACCG people had the highest pain response, attributed to low COMT function

Note that two of these SNPs are "silent" or synonymous variations, one is a promotor-region variation, and that the Val158Met variation, rs4680(G) appears in both the highest-function and lowest-function groups. This suggests an activity profile that is not affected by amino acid sequence, but perhaps rather by some quality of the RNA transcript. The study found similar quantities of RNA transcribed for all three haploblocks, but different levels of COMT function, suggesting that the mechanism may lie in translational efficiency.

[PMID 18698234] 4 SNPs affecting COMT activity were used to define low and high activity haplotypes. These SNPs are: rs6269, rs4633, rs4818, and rs4680. The mean levodopa dose increased in correspondence with the haplotype activity (low < medium < high). Doses prescribed for G-C-G-G (high activity) haplotype carriers (mean 604.2+/-261.9 mg) were significantly higher than those for the noncarriers (mean 512.2+/-133.5 mg, p<0.05).