Association study of cannabinoid receptor 1 (CNR1) gene in tardive dyskinesia.
Tardive dyskinesia (TD) is a severe, debilitating movement disorder observed in 25-30% of the patients treated with typical antipsychotics. Cannabinoid receptor 1 (CNR1) activators tend to inhibit movement, an effect prevented by rimonabant and other selective CNR1 antagonists. Furthermore, CNR1 receptor is downregulated in Huntington's disease and upregulated in Parkinson's disease. Twenty tagSNPs spanning the CNR1 gene were analyzed in schizophrenia patients of European ancestry (n=191; 74 with TD). Significant genotypic (P=0.012) and allelic (P=0.012) association was observed with rs806374 (T>C). Carriers of the CC genotype were more likely to be TD positive (CC vs TT+TC, odds ratio=3.4 (1.5-7.8), P=0.003) and had more severe TD (CC vs TT+TC; 9.52±9.2 vs 5.62±6.9, P=0.046). These results indicate a possible role of CNR1 in the development of TD in our patient population. However, these observations are marginal after correcting for multiple testing and need to be replicated in a larger patient population.
Neurogenetics Section, Neuroscience Department, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
A K
AK
Tiwari
C C
CC
Zai
O
O
Likhodi
A N
AN
Voineskos
H Y
HY
Meltzer
J A
JA
Lieberman
S G
SG
Potkin
G
G
Remington
D J
DJ
Müller
J L
JL
Kennedy
D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000009:adverse effects*; D016009:Chi-Square Distribution; D002908:Chronic Disease; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000209:etiology / Q000235:genetics*; D016017:Odds Ratio; D009864:Ontario / Q000453:epidemiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology; D012720:Severity of Illness Index; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics
D014150:Antipsychotic Agents; C571130:CNR1 protein, human; D043884:Receptor, Cannabinoid, CB1