Lack of association between MTHFR A1298C variant and Alzheimer's disease: evidence from a systematic review and cumulative meta-analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational genetic association studies
PubMed 28281392 · doi:10.1080/01616412.2017.1297340
What was done
Authors conducted a systematic review and cumulative meta-analysis across PubMed, Embase, China National Knowledge Infrastructure (CNKI), Google Scholar, and AlzGene databases. They evaluated the association between the MTHFR A1298C (rs1801131) polymorphism and Alzheimer's disease risk using odds ratios (ORs) and 95% confidence intervals (CIs) across five genetic models (allelic, homozygous, heterozygous, dominant, and recessive), alongside sensitivity analyses and publication bias assessments.
What was found
Ten eligible studies were included. No statistically significant association between MTHFR A1298C and Alzheimer's disease was observed in any tested genetic model: allelic (OR = 1.17, 95% CI: 0.88-1.56), homozygous (OR = 1.15, 95% CI: 0.87-1.53), heterozygous (OR = 1.19, 95% CI: 0.76-1.86), dominant (OR = 1.23, 95% CI: 0.81-1.87), and recessive (OR = 1.16, 95% CI: 0.89-1.52). Cumulative meta-analysis sorted by publication year also demonstrated a consistent pattern of no correlation.
Why it matters
This synthesis resolves prior ambiguity across conflicting individual studies by showing that the MTHFR A1298C polymorphism alone is unlikely to be a meaningful risk factor for Alzheimer's disease.
Limits
The analysis included only 10 studies, and the total participant count was not reported in the abstract. Potential gene-gene interactions, gene-environment interactions (such as folate intake), and population-specific ethnic differences were not detailed in the abstract.
Cited by
- contradicts MTHFR gene polymorphism is a significant risk factor for Alzheimer's disease.