Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism and Alzheimer Disease Risk: a Meta-Analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of case-control studies
PubMed 26820674 · doi:10.1007/s12035-016-9722-8
What was done
A meta-analysis of 41 case-control studies identified from PubMed, Google Scholar, Elsevier, and Springer Link databases through January 2015 investigating the link between the *MTHFR* C677T polymorphism and Alzheimer's disease (AD). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated across multiple genetic models using fixed-effect or random-effects models, with subgroup analyses performed by ethnicity.
What was found
The *MTHFR* C677T polymorphism was significantly associated with increased risk of AD across all evaluated genetic models: - Allelic model (T vs C): OR = 1.29, 95% CI 1.07–1.56, p = 0.003 - Dominant model (TT + CT vs CC): OR = 1.29, 95% CI 1.19–1.40, p = 0.0004 - Homozygote model (TT vs CC): OR = 1.31, 95% CI 1.16–1.48, p = 0.001 - Heterozygote model (CT vs CC): OR = 1.24, 95% CI 1.13–1.35, p < 0.004 - Recessive model (TT vs CT + CC): OR = 1.13, 95% CI 1.00–1.28, p = 0.02
Why it matters
This study aggregates conflicting case-control evidence to show that the *MTHFR* C677T variant is associated with a modest but statistically significant increase in susceptibility to Alzheimer's disease.
Limits
The abstract does not provide the total number of individuals analyzed, specific results of the ethnic subgroup analyses, or metrics of between-study heterogeneity and publication bias. The findings rely exclusively on retrospective case-control designs.
Cited by
- supports MTHFR gene polymorphism is a significant risk factor for Alzheimer's disease.