Genes of the Glutamatergic System and Tardive Dyskinesia in Patients with Schizophrenia

Abstract

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.

Роль Полиморфизма Генов Дофаминовой И Глутаматной Систем В Клинической Гетерогенности Шизофрении И Развитии Антипсихотик-Индуцированных Побочных Эффектов

“…Кроме того, у больных шизофренией обнаружена ассоциация между антипсихотик-индуцированной тардивной дискинезией и гаплотипом, состоящим из аллелей CAT полиморфных вариантов rs1042113, rs10768121 и rs12361171 гена SLC1A2 (табл. 1) [36].…”

The Role of Glutamatergic Gene Polymorphisms in the Clinical Phenotypes of Schizophrenia

“…Recently we demonstrated GRIN2A rs7206256 to be linked to the early manifestation of this disease [ 11 ]. Moreover, GRIN2A rs7192557 contributes to the development of antipsychotic induced limb-truncal tardive dyskinesia in patients with schizophrenia [ 12 ].…”

“…Studies showed associations between the SLC1A2 polymorphism and cognitive functions in patients with schizophrenia [ 16 , 18 , 19 ]. A haplotype of the SLC1A2 gene SNPs rs1042113, rs10768121, and rs12361171 was identified as a risk factor for tardive dyskinesia [ 12 ].…”