Association of C677T polymorphism (rs1801133) in MTHFR gene with depression.
Level 4 - case-series / case-control
Meta-analysis of observational case-control studies
PubMed 28968218 · doi:10.14715/cmb/2017.63.6.13
What was done
Authors conducted a meta-analysis of case-control studies investigating the relationship between the MTHFR C677T (rs1801133) polymorphism and depression risk. They searched four electronic databases (PubMed, Google Scholar, ScienceDirect, and SpringerLink) and included 30 studies comprising 4,802 depression cases and 17,362 controls. Five genetic models (additive, homozygote, dominant, recessive, and co-dominant) were evaluated.
What was found
Pooled analysis demonstrated statistically significant associations with depression risk across three genetic models: - Homozygote model (TT vs. CC): OR = 1.37 (95% CI: 1.13-1.65, p = 0.0004) - Additive model (T vs. C): OR = 1.20 (95% CI: 1.00-1.34, p = 0.0004) - Dominant model (TT+CT vs. CC): OR = 1.13 (95% CI: 0.99-1.28, p = 0.04) No significant associations were observed in the remaining two models: - Recessive model (TT vs. CT+CC): OR = 1.36 (95% CI: 0.91-2.04, p = 0.13) - Co-dominant model (CT vs. CC): OR = 1.00 (95% CI: 0.93-1.08, p = 0.84)
Why it matters
This review synthesizes two decades of conflicting genetic association literature, suggesting a weak but statistically detectable relationship between the MTHFR C677T polymorphism and depression risk.
Limits
All included data derive from retrospective case-control designs, which are prone to selection and publication biases. The abstract reports no subgroup analyses by ancestry, sex, age, or depression subtype, nor does it provide measures of between-study heterogeneity or evaluate environmental/dietary confounders (such as folate intake).
Cited by
- supports A pro-inflammatory MTHFR gene variant associated with depression risk is linked to increased survival against hepatitis B in sub-Saharan Africa.