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World J Biol Psychiatry. 2010 Sep;11(6):803-12. doi: 10.3109/15622975.2010.486043.

The catechol-O-methyl-transferase gene in tardive dyskinesia.

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Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.


Tardive dyskinesia (TD) is a severe and potentially irreversible motor side effect linked to long-term antipsychotic exposure. Changes in dopamine neurotransmission have been implicated in the etiology of TD, and catechol-O-methyl-transferase (COMT) is an enzyme that metabolizes dopamine.


We investigated five single-nucleotide polymorphisms in addition to the functional Val158Met variant spanning the COMT gene for association with TD.


We analyzed the six COMT single-nucleotide polymorphisms in a sample of schizophrenia/schizoaffective disorder patients (n=226; 196 Caucasians and 30 African Americans).


We found a significant association between the marker rs165599 in the 3' untranslated region of COMT and TD (AA versus G-carrier: OR(AA)=2.22, 95% CI:1.23-4.03; P=0.007). The association appeared to be originating from males. We did not find a significant association of the other five tested polymorphisms with TD in our samples. We performed a sex-stratified meta-analysis across all of the published studies (n=6 plus our own data) of COMT and TD, and found an association between ValVal genotype and TD in females (OR(ValVal)=1.63, 95% CI: 1.09-2.45; P=0.019) but not in males.


Overall, our results suggest that the COMT gene may have a minor but consistent role in TD, although sex-stratified studies with additional markers in larger clinical samples should be performed.

[Indexed for MEDLINE]

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