Association of Single-Nucleotide Polymorphisms in the Cannabinoid Receptor 2 Gene with Schizophrenia in the Han Chinese Population

Abstract

Cannabinoid receptor 2 (CNR2) is a major receptor in the endogenous cannabinoid system. In recent years, many studies have shown that the receptor is closely associated with schizophrenia. This study examined the relationship between CNR2 gene polymorphisms (rs2501432C/T, rs2229579C/T, rs2501401G/A) and schizophrenia. Three hundred sixteen schizophrenia patients and 334 healthy subjects were recruited as case and control groups, respectively. For rs2501432, the CT/TT genotype frequencies in the dominant model, TT genotype frequencies in the additive model, and T allele frequencies of the case group were lower than the control (P < 0.05), and the CT and TT genotypes and T allele frequencies of the male case group were significantly lower than the control (P < 0.05). For rs2229579, the T allele frequencies of the case group were higher than the control (P < 0.05). The T-C-G haplotype in the case group had a significantly lower frequency compared with the controls, but the T-T-A haplotype frequencies were higher in the case group than in the controls (P < 0.05). Our results suggest that the T allele of rs2501432 may be a protective factor, particularly in males, but the T allele of rs2229579 may be a risk factor for schizophrenia. T-C-G may be a protective haplotype for schizophrenia, but not the T-T-A haplotype.

Neuronal expression of CB2 cannabinoid receptor mRNAs in the mouse hippocampus

“…The deletion of CB2Rs in mice induces schizophrenia-like symptoms, such as impairment in sensory-motor gating, an increase in depressive behavior, and a deficit in long-term, passive avoidance memory (Ortega-Alvaro et al, 2011; Garcia-Gutierrez et al, 2013). In humans, the polymorphism of CNR2 is related to schizophrenia (Ishiguro et al, 2010; Tong et al, 2013), depression (Onaivi et al, 2008) and bipolar disorder (Minocci et al, 2011). Activation of CB2Rs reduces pain (for review, Anand et al, 2009) (but also see Brownjohn and Ashton, 2012), impulsive behaviors (Navarrete et al, 2012) and locomotor activity (Valenzano et al, 2005; Onaivi et al, 2008; Xi et al, 2011) of rodents, and also vomiting of ferrets (Van Sickle et al, 2005).…”

Deletion of CB2 cannabinoid receptors reduces synaptic transmission and long‐term potentiation in the mouse hippocampus

“…Chronic blockade of CB2Rs in rodents decreases anxiety (Garcia-Gutierrez et al, 2012). In humans, the polymorphism of CNR2, which encodes CB2R, is related to schizophrenia (Ishiguro et al, 2010;Tong et al, 2013), depression (Onaivi et al, 2008), and bipolar disorder (Minocci et al, 2011).…”

“…Whether and how CB2Rs modulate each of the induction, expression and maintenance stages of LTP need to be further studied. CB2Rs have been implicated in schizophrenia (Ishiguro et al, 2010;Tong et al, 2013), depression (Onaivi et al, 2008), and bipolar disorder (Minocci et al, 2011). Patients with schizophrenia display impaired functions of the hippocampus including memory deficits (Boyer et al, 2007).…”

CNR2 rs2229579 and COMT Val158Met variants, but not CNR2 rs2501432, IL-17 rs763780 and UCP2 rs659366, contribute to susceptibility to substance use disorder in the Turkish population

“…DNA was extracted from peripheral blood samples using a salting-out procedure [9]. The genotypes of COMT (Val108/158Met), CNR2 (rs2501432 and rs2229579), UCP2 (rs659366), and IL-17 (rs763780) gene variants were determined by the PCR-RFLP method as described by previous methods [10][11][12][13]. Primer sequences used and PCR conditions in the study are shown in Table 1.…”