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


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


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


RESULTS
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.


CONCLUSIONS
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.
Zai
Clement C
CC
Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Tiwari
Arun K
AK
Müller
Daniel J
DJ
De Luca
Vincenzo
V
Shinkai
Takahiro
T
Shaikh
Sajid
S
Ni
Xingqun
X
Sibony
David
D
Voineskos
Aristotle N
AN
Meltzer
Herbert Y
HY
Lieberman
Jeffrey A
JA
Potkin
Steven G
SG
Remington
Gary
G
Kennedy
James L
JL
D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000209:etiology / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*; D017678:Sex Distribution
D014150:Antipsychotic Agents; D002394:Catechol O-Methyltransferase