TY - JOUR
T1 - Genes of the Glutamatergic System and Tardive Dyskinesia in Patients with Schizophrenia
AU - Fedorenko, Olga Yu
AU - Paderina, Diana Z.
AU - Kornetova, Elena G.
AU - Poltavskaya, Evgeniya G.
AU - Pozhidaev, Ivan V.
AU - Goncharova, Anastasiia A.
AU - Freidin, Maxim B.
AU - Bocharova, Anna V.
AU - Bokhan, Nikolay A.
AU - Loonen, Anton J.M.
AU - Ivanova, Svetlana A.
N1 - Funding Information:
Funding: This work was conducted with the support of the Russian Science Foundation (project No. 21-15-00212).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
KW - antipsychotics
KW - genes
KW - glutamatergic system
KW - microglia
KW - pharmacogenetics
KW - schizophrenia
KW - tardive dyskinesia
UR - http://www.scopus.com/inward/record.url?scp=85133174896&partnerID=8YFLogxK
U2 - 10.3390/diagnostics12071521
DO - 10.3390/diagnostics12071521
M3 - Article
AN - SCOPUS:85133174896
SN - 2075-4418
VL - 12
JO - Diagnostics
JF - Diagnostics
IS - 7
M1 - 1521
ER -