Interactions Between Glycogen Synthase Kinase-3β Gene Polymorphisms, Negative Life Events, and Susceptibility to...

Background: Recent studies suggest that glycogen synthase kinase (GSK)-3β is involved in the development of major depressive disorder (MDD). The aim of this study was to investigate the interaction between GSK-3β polymorphism (rs6438552, rs334558, and rs2199503) and negative life events in the pathogenesis of major depressive disorder (MDD). Methods: DNA genotyping was performed on peripheral blood leukocytes in 550 patients with MDD and 552 age- and gender-matched controls. The frequency and severity of negative life events were assessed by the Life Events Scale (LES). A chi-square method was employed to assess the gene-environment interaction (G × E). Results: Differences in rs6438552, rs334558, and rs2199503 genotype distributions were observed between MDD patients and controls. Significant G × E interactions between allelic variation of rs6438552, rs334558, and rs2199503 and negative life events were observed. Individuals with negative life events and carrying genotypes of rs6438552 A⁺, rs334558 A⁺, and rs2199503G⁺ have increased the risk of depression. Conclusions: These results indicate that interactions between the GSK-3β rs6438552, rs334558, and rs2199503 polymorphisms and environment increases the risk of developing MDD.