The functional variant rs334558 of GSK3B is associated with remission in patients with depressive disorders

Abstract

Anastasia Levchenko,1,* Innokentiy S Losenkov,2,* Natalia M Vyalova,2 German G Simutkin,2 Nikolay A Bokhan,2,3 Bob Wilffert,4,5 Anton JM Loonen,4,6 Svetlana A Ivanova2,7 1Institute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg, Russia; 2Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia; 3Department of Psychotherapy and Psychological Counseling, National Research Tomsk State University, Tomsk, Russia; 4Groningen Research Institute of Pharmacy, University of Groningen, Groningen, the Netherlands; 5University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 6GGZ Westelijk Noord-Brabant, Bergen op Zoom, the Netherlands; 7Division for Control and Diagnostics, School of Non-Destructive Testing & Security, National Research Tomsk Polytechnic University, Tomsk, Russia *These authors contributed equally to this work Purpose: GSK3B and AKT1 genes have been implicated in the pathogenesis of a number of psychiatric and neurological disorders. Furthermore, their genetic variants are associated with response to antidepressant pharmacotherapy. As the evidence is still incomplete and inconsistent, continuing efforts to investigate the role of these two genes in the pathogenesis and treatment of brain disorders is necessary. The aim of our study was thus to evaluate the association of variants of these two genes with depressive disorders and drug treatment response.Patients and methods: In the present study, 222 patients with a depressive disorder who underwent pharmacological antidepressant treatment were divided into remitters and non-remitters following a 28-day course of pharmacotherapy. The association of a depressive disorder and remission rates with polymorphisms rs334558 in the GSK3B gene and rs1130214 and rs3730358 in the AKT1 gene was evaluated with a chi-square test.Results: Neither of the studied genetic variants was associated with a depressive disorder. Furthermore, frequencies of alleles and genotypes for rs1130214 and rs3730358 were not different in the groups of remitters and non-remitters. However, the activating allele T of the functional polymorphism rs334558 was significantly associated with remission, when all types of antidepressant drugs were included. This association continued as a trend when only patients taking selective serotonin reuptake inhibitors were considered.Conclusion: The present study provides support that the functional polymorphism rs334558 of GSK3B may play a role as a useful genetic and pharmacogenetic biomarker in the framework of personalized medicine approach. Keywords: depressive disorder, association study, AKT1, GSK3B, genetic biomarke