Lack of association between MTHFR A1298C variant and Alzheimer's disease: evidence from a systematic review and cumulative meta-analysis

Neurol Res. 2017 May;39(5):426-434. doi: 10.1080/01616412.2017.1297340. Epub 2017 Mar 10.

Abstract

Objectives: Previous studies have investigated the association between MTHFR A1298C (rs1801131) polymorphism and susceptibility to Alzheimer's disease (AD). Nevertheless, an ultimate conclusion remains obscure. We then executed this meta-analysis to estimate this association more precisely.

Methods: Related studies were systematically searched on PubMed, Embase, China National Knowledge Infrastructure, Google scholar, and AlzGene databases. The association was evaluated by reviewing the odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Publication bias, sensitivity analysis, and cumulative meta-analysis were performed to help draw a more definite conclusion.

Results: Ten eligible studies were finally enrolled in this meta-analysis. Lack of association between MTHFR A1298C polymorphism and AD risk was observed in five genetic models (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; recessive: OR = 1.16, 95% CI: 0.89-1.52). The result of cumulative meta-analysis sorted by publication year was also detected a dynamic tendency of no correlation between MTHFR A1298C polymorphism and AD.

Conclusion: This meta-analysis reveals that MTHFR A1298C polymorphism may not be associated with AD risk.

Keywords: A1298C (rs1801131) polymorphism; Alzheimer’s disease; Methylene-tetrahydrofolate reductase (MTHFR); meta-analysis.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Alanine / genetics
  • Alzheimer Disease / genetics*
  • Cysteine / genetics
  • Genetic Association Studies
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Polymorphism, Single Nucleotide / genetics*

Substances

  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Cysteine
  • Alanine