Back to Journals » The Application of Clinical Genetics » Volume 13

Association of Cholinergic Muscarinic M4 Receptor Gene Polymorphism with Schizophrenia

Authors Pozhidaev IV, Boiko AS, Loonen AJM, Paderina DZ, Fedorenko OY, Tenin G, Kornetova EG, Semke AV, Bokhan NA, Wilffert B, Ivanova SA

Received 25 January 2020

Accepted for publication 2 April 2020

Published 22 April 2020 Volume 2020:13 Pages 97—105


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Martin H. Maurer

Ivan V Pozhidaev,1,2 Anastasiia S Boiko,1 Anton JM Loonen,3 Diana Z Paderina,1,2 Olga Yu Fedorenko,1,4 Gennadiy Tenin,5 Elena G Kornetova,1,6 Arkadiy V Semke,1 Nikolay A Bokhan,1,2,6 Bob Wilffert,3,7 Svetlana A Ivanova1,4,6

1Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russian Federation; 2National Research Tomsk State University, Tomsk, Russian Federation; 3Unit of PharmacoTherapy, Epidemiology & Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands; 4National Research Tomsk Polytechnic University, Tomsk, Russian Federation; 5Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK; 6Siberian State Medical University, Tomsk, Russian Federation; 7Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

Correspondence: Anton JM Loonen
University of Groningen, Groningen Research Institute of Pharmacy, PharmacoTherapy, Epidemiology & Economics, Antonius Deusinglaan 1, Groningen 9713AV, the Netherlands
Tel +31 50 363 7576
Fax +31 50 363 2772

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

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]