Dataset Information

A major single nucleotide polymorphism of the PDLIM5 gene associated with recurrent major depressive disorder.

ABSTRACT: OBJECTIVE: The PDLIM5 gene is known to interact specifically with the N-type calcium channel alpha-1B subunit and protein kinase C epsilon and is critical for rapid, efficient potentiation of the calcium channel activation by protein kinase C in neurons. Increasing amounts of data suggested that PDLIM5 might be involved in the pathophysiology of major depressive disorder (MDD). The aim of this study was to examine whether genetic variations in the human PDLIM5 gene might contribute to the liability to develop MDD. METHOD: We undertook a gene-based association analysis of single nucleotide polymorphisms (SNPs). Three SNPs (rs10008257, rs2433320 and rs2452600) were identified in the PDLIM5 gene and genotyped in patients diagnosed with recurrent MDD and in matched control subjects. RESULTS: We observed significant allele (p = 0.007) and genotype (p = 0.007) association with rs2433320, and the G allele of rs2433320 was significantly overrepresented in control subjects in comparison with MDD patients. CONCLUSION: These results support the hypothesis of a protective effect for the G allele of rs2433320 in the PDLIM5 gene in recurrent MDD.

SUBMITTER: Liu Z

PROVIDER: S-EPMC2186365 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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A major single nucleotide polymorphism of the PDLIM5 gene associated with recurrent major depressive disorder.

Liu Zhongchun Z Liu Wanhong W Xiao Zheman Z Wang Gaohua G Yin Shijin S Zhu Fan F Wang Huiling H Cheng Jin J Wang Xiaoping X He Xiaohua X Li Wenxin W

Journal of psychiatry & neuroscience : JPN 20080101 1

<h4>Objective</h4>The PDLIM5 gene is known to interact specifically with the N-type calcium channel alpha-1B subunit and protein kinase C epsilon and is critical for rapid, efficient potentiation of the calcium channel activation by protein kinase C in neurons. Increasing amounts of data suggested that PDLIM5 might be involved in the pathophysiology of major depressive disorder (MDD). The aim of this study was to examine whether genetic variations in the human PDLIM5 gene might contribute to the ...[more]

PMID: 18197271

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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

A major single nucleotide polymorphism of the PDLIM5 gene associated with recurrent major depressive disorder.

Publications

A major single nucleotide polymorphism of the PDLIM5 gene associated with recurrent major depressive disorder.

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