Association of the MscI polymorphism of the dopamine D3 receptor gene with tardive dyskinesia in schizophrenia.
In 112 schizophrenic patients previously treated with typical neuroleptics, we investigated the putative role of the dopamine D3 receptor gene (DRD3) in tardive dyskinesia (TD). Patients were assessed for TD severity using the Abnormal Involuntary Movement Scale (AIMS) and were subsequently genotyped for the MscI polymorphism that identifies a serine to glycine substitution in DRD3. A modified analysis of covariance model, which incorporated several clinical risk factors for TD, was utilized to detect differences in TD severity among the various genotypic groups. The glycine allele of DRD3 was found to be associated with typical neuroleptic-induced TD (F[2,95] = 8.25, p < .0005). Higher mean AIMS scores were found in patients homozygous for the glycine variant of the DRD3 gene, as compared to both heterozygous and serine homozygous patients. Although replication is necessary, this finding supports a role for the dopamine D3 receptor in the pathogenesis of TD.
Basile
V S
VS
Neurogenetics Section, Clarke Institute of Psychiatry, University of Toronto, Canada.
Masellis
M
M
Badri
F
F
Paterson
A D
AD
Meltzer
H Y
HY
Lieberman
J A
JA
Potkin
S G
SG
Macciardi
F
F
Kennedy
J L
JL
D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D014150:Antipsychotic Agents / Q000009:adverse effects; D044383:Black People / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics*; D004409:Dyskinesia, Drug-Induced / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3; D012307:Risk Factors; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D044465:White People / Q000235:genetics
D014150:Antipsychotic Agents; C493593:DRD3 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D015252:Deoxyribonucleases, Type II Site-Specific; C060616:TGGCCA-specific type II deoxyribonucleases