Korean J Biol Psychiatry.  2014 Aug;21(3):99-106.

Association Analysis between (AAT)n Repeats in the Cannabinoid Receptor 1 Gene and Schizophrenia in a Korean Population

• Kim JW
• Roh YH
• Kim MJ
• Kim CR
• Park BL
• Bae JS
• Shin HD
• Choi IG
• Han SW
• Hwang J
• Woo SI

Abstract

OBJECTIVES
Previous studies suggest that the cannabinoid receptor 1 (CNR1) gene could be an important candidate gene for schizophrenia. According to linkage studies, this gene is located on chromosome 6q14-q15, which is known to harbor the schizophrenia susceptibility locus (locus 5, SCZ5, OMIM 803175). The pharmacological agent delta-9-tetrahydrocannabinol (Delta-9-THC) seems to elicit the symptoms of schizophrenia. The association between CNR1 polymorphisms and schizophrenia is actively being investigated, and some studies have linked the AAT-trinucleotide repeats in CNR1 to the onset of schizophrenia. In this study, we have investigated the association between the AAT-trinucleotide repeats in CNR1 and schizophrenia by studying schizophrenia patients and healthy individuals from Korea.
METHODS
DNA was extracted from the blood samples of 394 control subjects and 337 patients diagnosed with schizophrenia (as per the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria). After polymerase chain reaction amplification, a logistic regression analysis, with age and gender as the covariates, was performed to study the variations in the AAT-repeat polymorphisms between the two groups.
RESULTS
In total, 8 types of trinucleotide repeats were identified, each containing 7, 8, 10, 11, 12, 13, 14, and 15 repeats, respectively. (AAT)13 allele was most frequently observed, with a frequency of 33.6% and 31.6% in the patient and control groups, respectively. The frequency of the other repeat alleles in the patient group (in the decreasing order) was as follows : (AAT)13 33.6%, (AAT)14 21.6%, (AAT)12 18.5%, and (AAT)7 11.1%. The frequency of the repeat alleles in the control group (in the decreasing order) was as follows : (AAT)13 31.6%, (AAT)14 24.5%, (AAT)12 17.2%, and (AAT)7 11.6%. However, there were no significant differences in the AAT-repeat polymorphisms of the CNR1 gene between the patient group and the control group.
CONCLUSIONS
Although our study revealed no significant association of the AAT-repeat polymorphism of the CNR1 gene with schizophrenia, it will serve as a good reference for future studies designed to examine the cannabinoid hypothesis of schizophrenia.

Keyword

Schizophrenia; Cannabinoid receptor 1 gene; AAT repeats polymorphism