Association between MTHFR C677T polymorphism and depression: An updated meta-analysis of 26 studies

Background: Previous studies concerning the association between the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and depression have provided inconclusive findings. A meta-analysis was therefore performed to investigate a more reliable estimate.

Methods: This meta-analysis recruited 26 published studies which were selected by a search of electronic databases up to January 2013, including 4992 depression cases and 17,082 controls. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between MTHFR C677T polymorphism and depression susceptibility using random effect models.

Results: Meta-analyses results suggested that MTHFR C677T polymorphism contributed to the increased depression risk in overall populations (for T vs. C: OR=1.19, 95%CI=1.07-1.32; for TT+CT vs. CC: OR=1.15, 95%CI=1.01-1.31; for TT vs. CC: OR=1.42, 95%CI=1.16-1.75; for TT vs. CT+CC: OR=1.38, 95%CI=1.16-1.63). Subgroup analysis by ethnicity indicated an association in Asian populations (for T vs. C: OR=1.36, 95%CI=1.11-1.66; for TT+CT vs. CC: OR=1.32, 95%CI=1.03-1.69; for TT vs. CC: OR=1.88, 95%CI=1.26-2.79; for TT vs. CT+CC: OR=1.76, 95%CI=1.30-2.38); and a marginal association in White populations (for TT vs. CT+CC: OR=1.15, 95%CI=1.01-1.31). However, the association between the MTHFR C677T polymorphism and depression was not observed in the elderly.

Conclusion: The MTHFR C677T polymorphism was associated with an increased risk of depression, especially in Asian populations. However, there was no evidence indicating a correlation in the elderly.