Methylenetetrahydrofolate Reductase A1298C Polymorphism and Major Depressive Disorder.

Kevin Cho,Saeed K Alzghari,Jie An,Kerry Anne Rambaran,Tyler B Johnson,Zubair M Amin

doi:10.7759/cureus.1734

Kevin Cho, Saeed K Alzghari + Show 4 more

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https://doi.org/10.7759/cureus.1734

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Journal: Cureus	Publication Date: Oct 1, 2017
Citations: 9	License type: cc-by

Affiliation: Keck Graduate Institute, University of the Pacific

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.

Highlights

Major depressive disorder (MDD) or clinical depression, is a mental disorder characterized by a persistent feeling of hopelessness or despair and a general loss of interest in daily activities
In 2015, nearly 16 million adults in the United States (U.S.) had experienced MDD within the previous year, and this number accounts for approximately 7% of all adults in the U.S [2]
A transversion at nucleotide 1298 in exon 7 on the methylenetetrahydrofolate reductase (MTHFR) gene leads to a 60% reduction in enzyme activity compared to the wild-type enzyme [12]

Summary

Introduction

Major depressive disorder (MDD) or clinical depression, is a mental disorder characterized by a persistent feeling of hopelessness or despair and a general loss of interest in daily activities. By genotyping 136 female patients and 284 controls in a study by Reif, et al, A1298C was determined to be significantly associated with both MDD and bipolar disorder whereas C677T. The study, noted that the strong association was found only in female patients and controls with higher statistical power than the previous studies Based on these findings, A1298C has the potential to be an alternative or complementary, gender-specific indicator in diagnosing MDD in the Caucasian population. While the MTHFR gene has the potential to predict MDD prognosis by assessing both SNPs, their strong correlation yet remains to be elucidated These studies suggest that the prognosis may not depend solely on reduced enzyme activity. Despite the controlled folate intake, vascular dysfunction manifests into psychiatric symptoms which place the elderly population more at risk for poorer outcomes related to diet and genetic differences in folate genes [8, 11, 24]

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