title: The catechol-O-methyl-transferase gene in tardive dyskinesia.
abstract: 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.
authors.affiliation: Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Clement C
authors.initials: CC
authors.lastname: Zai
authors.forename: Arun K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shinkai
authors.forename: Sajid
authors.initials: S
authors.lastname: Shaikh
authors.forename: Xingqun
authors.initials: X
authors.lastname: Ni
authors.forename: David
authors.initials: D
authors.lastname: Sibony
authors.forename: Aristotle N
authors.initials: AN
authors.lastname: Voineskos
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: Steven G
authors.initials: SG
authors.lastname: Potkin
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: 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
chemical_list: D014150:Antipsychotic Agents; D002394:Catechol O-Methyltransferase