Genes of the Glutamatergic System and Tardive Dyskinesia in Patients with Schizophrenia
Olga Yu. Fedorenko,
Diana Z. Paderina,
Elena G. Kornetova,
Evgeniya G. Poltavskaya,
Ivan V. Pozhidaev,
Anastasiia A. Goncharova,
Maxim B. Freidin,
Anna V. Bocharova,
Nikolay A. Bokhan,
Anton J. M. Loonen,
Svetlana A. Ivanova
Affiliations
Olga Yu. Fedorenko
Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia
Diana Z. Paderina
Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia
Elena G. Kornetova
Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia
Evgeniya G. Poltavskaya
Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia
Ivan V. Pozhidaev
Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia
Anastasiia A. Goncharova
Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia
Maxim B. Freidin
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, Russia
Anna V. Bocharova
Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, Russia
Nikolay A. Bokhan
Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia
Anton J. M. Loonen
Unit of PharmacoTherapy, Epidemiology & Economics, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands
Svetlana A. Ivanova
Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia
Background: Tardive dyskinesia (TD) is an extrapyramidal side effect of the long-term use of antipsychotics. In the present study, the role of glutamatergic system genes in the pathogenesis of total TD, as well as two phenotypic forms, orofacial TD and limb-truncal TD, was studied. Methods: A set of 46 SNPs of the glutamatergic system genes (GRIN2A, GRIN2B, GRIK4, GRM3, GRM7, GRM8, SLC1A2, SLC1A3, SLC17A7) was studied in a population of 704 Caucasian patients with schizophrenia. Genotyping was performed using the MassARRAY Analyzer 4 (Agena Bioscience™). Logistic regression analysis was performed to test for the association of TD with the SNPs while adjusting for confounders. Results: No statistically significant associations between the SNPs and TD were found after adjusting for multiple testing. Since three SNPs of the SLC1A2 gene demonstrated nominally significant associations, we carried out a haplotype analysis for these SNPs. This analysis identified a risk haplotype for TD comprising CAT alleles of the SLC1A2 gene SNPs rs1042113, rs10768121, and rs12361171. Nominally significant associations were identified for SLC1A3 rs2229894 and orofacial TD, as well as for GRIN2A rs7192557 and limb-truncal TD. Conclusions: Genes encoding for mGlu3, EAAT2, and EAAT1 may be involved in the development of TD in schizophrenia patients.
