Methylenetetrahydrofolate Reductase A1298C Polymorphism and Major Depressive Disorder

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.