Analysis of genetic variations in the RGS9 gene and antipsychotic-induced tardive dyskinesia in schizophrenia.
Some patients treated chronically with antipsychotics develop tardive dyskinesia (TD), an abnormal involuntary movement disorder. Typical antipsychotics block D(2) dopamine receptors (D(2)DR) and produce D(2)DR supersensitivity. On contrary, regulators of G-protein signaling (RGS) can enhance the signal termination of G-protein-coupled D(2)DR. Besides, after prolonged inhibition of dopaminergic transmission, dopaminergic agonists induced severe dyskinesia only in RGS9 knock-out mice but not in normal mice. Therefore, variety in the human RGS9 gene may be related to susceptibility to TD. In this study, schizophrenic inpatients receiving long-term antipsychotic treatment were assessed using the Abnormal Involuntary Movement Scale twice over a 3-month interval. Only patients in whom abnormal involuntary movements were absent (non-TD group) and those who showed persistent TD (TD group) were enrolled. There were 407 patients in the study sample (TD = 252; non-TD = 155) and seven single nucleus polymorphisms (SNPs) in the RGS9 gene were genotyped for each subject. Genotype and allelic distributions of SNPs did not differ between the TD and non-TD groups in this study, with the exception that a weak trend of allelic association was seen with rs4790953 (P = 0.0399). In the haplotype analysis, a significant association of the AGG haplotype (rs8077696-rs8070231-rs2292593) of the RGS9 gene was found (permutation P = 0.007), and this is worthy of replication and further study.
Liou
Ying-Jay
YJ
Department of Psychiatry, Taipei Veterans General Hospital, Taiwan.
Chen
Mao-Liang
ML
Wang
Ying-Chieh
YC
Chen
Jen-Yeu
JY
Liao
Ding-Lieh
DL
Bai
Ya-Mei
YM
Lin
Chao-Cheng
CC
Chen
Tzu-Ting
TT
Mo
Geng-Han
GH
Lai
I-Ching
IC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004409:Dyskinesia, Drug-Induced / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020710:RGS Proteins / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy*; D055815:Young Adult
D014150:Antipsychotic Agents; D020710:RGS Proteins; C116925:regulator of g-protein signaling 9