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Association study of three single-nucleotide polymorphisms in the cyclic adenosine monophosphate response element binding 1 gene and major depressive disorder.

ABSTRACT: Major depressive disorder is a common chronic emotional disorder, and cyclic adenosine monophosphate response element binding protein 1 (CREB1) is hypothesized to play a role in its pathogenesis. The aim of the present study was to investigate the associations between major depressive disorder and relevant single nucleotide polymorphisms (SNPs) in the CREB1 gene. A total of 1,038 subjects of Han Chinese descent were recruited, including 456 patients with major depressive disorder (case group) and 582 healthy volunteers (control group). The frequency distributions of the genotypes and alleles were estimated in the case and control groups, and analyzed for any correlation with major depressive disorder. Three relevant SNP sites in CREB1 were analyzed using quantitative polymerase chain reaction, and statistical analyses were performed to estimate their use as risk factors for major depressive disorder. The analyses revealed that rs2254137 and rs16839883 in CREB1 showed polymorphisms in the sample population, and the genotype and allele frequencies of rs16839883 differed significantly when comparing the patients and healthy controls (P<0.05). No statistically significant differences were detected in the two SNP sites between the male and female patients (P>0.05). Furthermore, no statistically significant differences were detected in rs2254137 genotype and allele distribution when comparing the male and female patients with their corresponding control groups (P>0.05). However, statistically significant differences were observed in the genotype and allele frequencies of rs16839883 when the male and female patients were compared with their respective controls (P<0.05). Therefore, the results demonstrated that there is a close correlation between the rs16839883 polymorphism in CREB1 and major depressive disorder, which suggests that this SNP site should be further studied as a potential biomarker for major depressive disorder.

SUBMITTER: Wei Y

PROVIDER: S-EPMC4473368 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Association study of three single-nucleotide polymorphisms in the cyclic adenosine monophosphate response element binding 1 gene and major depressive disorder.

Wei Yange Y Bu Shufang S Liu Xican X Li Hengfen H

Experimental and therapeutic medicine 20150403 6

Major depressive disorder is a common chronic emotional disorder, and cyclic adenosine monophosphate response element binding protein 1 (CREB1) is hypothesized to play a role in its pathogenesis. The aim of the present study was to investigate the associations between major depressive disorder and relevant single nucleotide polymorphisms (SNPs) in the CREB1 gene. A total of 1,038 subjects of Han Chinese descent were recruited, including 456 patients with major depressive disorder (case group) an ...[more]

PMID: 26136966

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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

Association study of three single-nucleotide polymorphisms in the cyclic adenosine monophosphate response element binding 1 gene and major depressive disorder.

Publications

Association study of three single-nucleotide polymorphisms in the cyclic adenosine monophosphate response element binding 1 gene and major depressive disorder.

Similar Datasets

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