Association analysis of polymorphisms in the N-methyl-D-aspartate (NMDA) receptor subunit 2B (GRIN2B) gene and tardive dyskinesia in schizophrenia.
Tardive dyskinesia (TD) is a neurological disorder characterized by irregular, non-rhythmic, choreoathetotic and involuntary movements in single or multiple body regions. Chronic administration of typical antipsychotic agents, which predominantly act on dopamine receptors, implicates the dopamine system in susceptibility to TD. An alternative to this dopaminergic supersensivity hypothesis in understanding the pathogenesis of TD is the glutamatergic neurotoxicity hypothesis, which implicates the N-methyl-D-aspartate (NMDA) receptor in TD pathogenesis. In the present study, the association between three polymorphisms (T-200G, C366G and C2664T) of the GRIN2B gene, which encodes the 2B subunit of the NMDA receptor, and the occurrence and severity of TD were investigated in 273 Chinese schizophrenic patients receiving long-term antipsychotic treatment (TD: 142, non-TD: 133). There was no significant association between patients' genotype and allele frequencies and TD occurrence. Among the TD patients, the differences in the total scores on the Abnormal Involuntary Movement Scale (AIMS) among the three genotypes of each polymorphism were not significant. Because the three studied markers are in weak linkage disequilibrium with each other, haplotype-based association was not carried out. We conclude that genetic variations in the human GRIN2B gene probably do not play a major role in susceptibility to, or severity of TD.
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Ying-Jay
YJ
Liou
Ying-Chieh
YC
Wang
Jen-Yeu
JY
Chen
Ya-Mei
YM
Bai
Chao-Cheng
CC
Lin
Ding-Lieh
DL
Liao
Tzu-Ting
TT
Chen
Mao-Liang
ML
Chen
Geng-Han
GH
Mo
I-Ching
IC
Lai
D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D004409:Dyskinesia, Drug-Induced / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010808:Physical Examination; D011110:Polymorphism, Genetic; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics; D012720:Severity of Illness Index
D014150:Antipsychotic Agents; D005819:Genetic Markers; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate