Analysis of genetic variations in the human melatonin receptor (MTNR1A, MTNR1B) genes and antipsychotics-induced tardive dyskinesia in schizophrenia.
OBJECTIVE
Antipsychotics-induced tardive dyskinesia (TD) has been suggested to be related to altered dopaminergic neurotransmission in the striatum. Melatonin has a modulating effect on dopaminergic neurotransmission in the brain; therefore, the hypothesis of an association between the melatonin receptor genes (MTNR1A, MTNR1B) and antipsychotics-induced TD was examined in this study.


METHODS
Schizophrenic inpatients receiving long-term antipsychotic treatment were assessed using the Abnormal Involuntary Movement Scale, and only patients who were either free of any abnormal involuntary movement (non-TD group) or who demonstrated persistent TD (TD group) were enrolled. Genotyping of six tagging single nucleus polymorphisms (SNPs) in the melatonin receptor genes (MRNR1A, MTNR1B) was then performed for each subject.


RESULTS
Four hundred and eighteen inpatients (TD=256, non-TD=162) fitted the study criteria and underwent TD assessment and genotyping. Individual haplotype analysis showed that the haplotype ATG was significantly associated with non-TD (permutation P=0.037), and the association was also found to be significant by global haplotype analyses (permutation P=0.045).


CONCLUSIONS
Our results indicated a significant association between the haplotype ATG in the MTNR1A gene and non-TD. Further replication in other countries or other populations is indicated.
Lai
I-Ching
IC
Department of Psychiatry, Tzu Chi General Hospital, Hualien, 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
Liou
Ying-Jay
YJ
D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004409:Dyskinesia, Drug-Induced / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044094:Receptors, Melatonin / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*
D014150:Antipsychotic Agents; D044094:Receptors, Melatonin