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Methylenetetrahydrofolate Reductase A1298C Polymorphism and Major Depressive Disorder.

ABSTRACT: Major depressive disorder (MDD) is a disorder that carries significant psychosocial and economic implications. Research efforts have focused on identifying biomarkers that can aid in the prediction, diagnosis, and efficacious treatment of MDD. Most of this focus has been placed on a polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene, C677T. MTHFR C677T is screened during MDD diagnosis in many protocols. However, MTHFR C667T poses conflicting data in various ethnic groups and geographic populations calling into question its utility. Another polymorphism, MTHFR A1298C, has often taken the back-seat to MTHFR C677T in respect to research focus. MTHFR A1298C is implicated in irregular homocysteine metabolism and aberrant folate cycles and, through this, it may play a role as either a driver in the development of MDD or as a predictive or diagnostic marker, possibly in combination with C677T. The number of studies evaluating MTHFR A1298C and the power of those studies is lacking and thus larger studies are required to confirm the association between this polymorphism and MDD.

SUBMITTER: Cho K

PROVIDER: S-EPMC5711500 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Methylenetetrahydrofolate Reductase A1298C Polymorphism and Major Depressive Disorder.

Cho Kevin K Amin Zubair M ZM An Jie J Rambaran Kerry Anne KA Johnson Tyler B TB Alzghari Saeed K SK

Cureus 20171001 10

Major depressive disorder (MDD) is a disorder that carries significant psychosocial and economic implications. Research efforts have focused on identifying biomarkers that can aid in the prediction, diagnosis, and efficacious treatment of MDD. Most of this focus has been placed on a polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene, C677T. MTHFR C677T is screened during MDD diagnosis in many protocols. However, MTHFR C667T poses conflicting data in various ...[more]

PMID: 29209581

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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

Methylenetetrahydrofolate Reductase A1298C Polymorphism and Major Depressive Disorder.

Publications

Methylenetetrahydrofolate Reductase A1298C Polymorphism and Major Depressive Disorder.

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