Dataset Information

Interactions Between Glycogen Synthase Kinase-3? Gene Polymorphisms, Negative Life Events, and Susceptibility to Major Depressive Disorder in a Chinese Population.

ABSTRACT: Background: Recent studies suggest that glycogen synthase kinase (GSK)-3? is involved in the development of major depressive disorder (MDD). The aim of this study was to investigate the interaction between GSK-3? 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-3? rs6438552, rs334558, and rs2199503 polymorphisms and environment increases the risk of developing MDD.

SUBMITTER: Yang J

PROVIDER: S-EPMC7917206 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Interactions Between Glycogen Synthase Kinase-3β Gene Polymorphisms, Negative Life Events, and Susceptibility to Major Depressive Disorder in a Chinese Population.

Yang Jiarun J Ke Siyuan S Qiao Zhengxue Z Yang Xiuxian X Qiu Xiaohui X Song Xuejia X Zhao Erying E Zhou Jiawei J Zhao Mingzhe M Yang Yanjie Y Fang Deyu D Cao Depin D

Frontiers in psychiatry 20210215

<b>Background:</b> 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). <b>Methods:</b> DNA genotyping was performed on peripheral blood leukocytes in 550 patients with MDD and 552 age- and gender-matched controls. The fr ...[more]

PMID: 33658947

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Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Dataset Information

Interactions Between Glycogen Synthase Kinase-3? Gene Polymorphisms, Negative Life Events, and Susceptibility to Major Depressive Disorder in a Chinese Population.

Publications

Interactions Between Glycogen Synthase Kinase-3β Gene Polymorphisms, Negative Life Events, and Susceptibility to Major Depressive Disorder in a Chinese Population.

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