TY - JOUR

T1 - The functional variant RS334558 of GSK3B is associated with remission in patients with depressive disorders

AU - Levchenko, Anastasia

AU - Losenkov, Innokentiy S.

AU - Vyalova, Natalia M.

AU - Simutkin, German G.

AU - Bokhan, Nikolay A.

AU - Wilffert, Bob

AU - Loonen, Anton J.M.

AU - Ivanova, Svetlana A.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - AKT1

KW - Association study

KW - Depressive disorder

KW - Genetic biomarker

KW - GSK3B

UR - http://www.scopus.com/inward/record.url?scp=85050518678&partnerID=8YFLogxK

U2 - 10.2147/PGPM.S171423

DO - 10.2147/PGPM.S171423

M3 - Article

AN - SCOPUS:85050518678

VL - 11

SP - 121

EP - 126

JO - Pharmacogenomics and Personalized Medicine

JF - Pharmacogenomics and Personalized Medicine

SN - 1178-7066

ER -