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Prog Neuropsychopharmacol Biol Psychiatry. 2013 Oct 1;46:78-85. doi: 10.1016/j.pnpbp.2013.06.015. Epub 2013 Jul 4.

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

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Department of Epidemiology and Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan road, Hefei, Anhui 230032, China.



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.


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.


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.


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.


5,10-methylenetetrahydrofolate reductase; CIs; Depression; HWE; Hardy–Weinberg equilibrium; MTHFR; Meta-analysis; Methylenetetrahydrofolate reductase; ORs; Odds ratios; Polymorphism; confidence intervals

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