title: Association study of tardive dyskinesia and twelve DRD2 polymorphisms in schizophrenia patients.
abstract: Tardive dyskinesia (TD) is a side-effect of chronic antipsychotic medication. Abnormalities in dopaminergic activity in the nigrostriatal system have been most often suggested to be involved because the agents which cause TD share in common potent antagonism of dopamine D2 receptors (DRD2), that notably is not balanced by effects such as more potent serotonin (5-HT)2A antagonism. Thus, a number of studies have focused on the association of dopamine system gene polymorphisms and TD. The most consistent findings have been found with the Ser9Gly polymorphism of the DRD3 gene. Although DRD2 has long been hypothesized to be the main target for antipsychotics, only a few polymorphisms in DRD2 have been investigated for their potential involvement in the aetiology of TD. In the present study, we investigated 12 polymorphisms spanning the DRD2 gene and their association with TD in our European Caucasian (n=202) and African-American (n=30) samples. Genotype frequencies for a functional polymorphism, C957T (Duan et al., 2003; Hirvonen et al., 2004), and the adjacent C939T polymorphism were found to be significantly associated with TD (p=0.013 and p=0.022 respectively). DRD2 genotypes were not significantly associated with TD severity as measured by AIMS (Abnormal Involuntary Movement Scale) with the exception of a trend for C939T (p=0.071). Both TD and total AIMS scores were found to be significantly associated with two-marker haplotypes containing C939T and C957T (p=0.021 and p=0.0087 respectively). Preliminary results indicated that C957T was also associated with TD in our African-American sample (p=0.047). Taken together, the present study suggests that DRD2 may be involved in TD in the Caucasian population, although further studies are warranted.
authors.affiliation: Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Clement C
authors.initials: CC
authors.lastname: Zai
authors.forename: Rudi W
authors.initials: RW
authors.lastname: Hwang
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
authors.forename: Nicole
authors.initials: N
authors.lastname: King
authors.forename: Gwyneth C
authors.initials: GC
authors.lastname: Zai
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
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: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D001741:Black or African American; D014150:Antipsychotic Agents / Q000009:adverse effects; D016009:Chi-Square Distribution; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics; D044465:White People
chemical_list: D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2