Association of Cholinergic Muscarinic M4 Receptor Gene Polymorphism with Schizophrenia

Abstract

Background

Previous studies have linked muscarinic M4 receptors (CHRM4) to schizophrenia. Specifically, the rs2067482 polymorphism was found to be highly associated with this disease.

Purpose

To test whether rs2067482 and rs72910092 are potential risk factors for schizophrenia and/or pharmacogenetic markers for antipsychotic-induced tardive dyskinesia.

Patients and Methods

We genotyped DNA of 449 patients with schizophrenia and 134 healthy controls for rs2067482 and rs72910092 polymorphisms of the CHRM4 gene with the use of the MassARRAY^® System by Agena Bioscience. Mann–Whitney test was used to compare qualitative traits and χ² test was used for categorical traits.

Results

The frequency of genotypes and alleles of rs72910092 did not differ between patients with schizophrenia and control subjects. We did not reveal any statistical differences for both rs2067482 and rs72910092 between schizophrenia patients with and without tardive dyskinesia. The frequency of the C allele of the polymorphic variant rs2067482 was significantly higher in healthy persons compared to patients with schizophrenia (OR=0.51, 95% CI [0.33–0.80]; p=0.003). Accordingly, the CC genotype was found significantly more often in healthy persons compared to patients with schizophrenia (OR=0.49, 95% CI [0.31–0.80]; p=0.010).

Conclusion

Our study found the presence of the minor allele (T) of rs2067482 variant being associated with schizophrenia. We argue that the association of rs2067482 with schizophrenia may be via its regulatory effect on some other gene with protein kinase C and casein Kknase substrate in neurons 3 (PACSIN3) as a possible candidate. Neither rs2067482 nor rs72910092 is associated with tardive dyskinesia.

Keywords:

• schizophrenia
• suicide
• tardive dyskinesia
• PACSIN3
• CHRM4
• gene polymorphism

Acknowledgments

This work resulted from a collaboration between the Mental Health Research Institute in Tomsk and the Groningen Research Institute of Pharmacy (GRIP) of the University of Groningen. The Russian part is carried out within the framework of the Tomsk Polytechnic University Competitiveness Enhancement Program, which did not provide financial assistance for research.

Disclosure

The authors report no conflicts of interest in this work.