MTHFR C677T polymorphism and migraine risk: a meta-analysis

J Neurol Sci. 2014 Jan 15;336(1-2):68-73. doi: 10.1016/j.jns.2013.10.008. Epub 2013 Oct 11.


Many molecular epidemiological studies were carried out in recent years to assess the association between the MTHFR C677T polymorphism and migraine risk in diverse populations. However, the results remain controversial rather than conclusive. The objective of this study was to investigate the role of C677T MTHFR polymorphism in migraine pathogenesis. We performed a meta-analysis of published case-control studies concerning the association of the C677T MTHFR polymorphism and migraine. Pooled ORs were established using both random and fixed effects models. This meta-analysis on 17 studies with 8903 cases and 27,637 controls showed that the allele 677T was associated with a significantly increased risk of total migraine in Asians (TT vs. CT+CC: OR=1.62, 95% CI: 1.13-2.32, P(H)=0.573, I(2)=0.0%; T vs. C: OR=1.18, 95% CI: 1.00-1.40, P(H)=0.147, I(2)=44.1%). Similar results were also presented in Asian populations with MA (TT vs. CC: OR=1.62, 95% CI: 1.11-3.75; TT vs. CT+CC: OR=2.00, 95% CI: 1.01-3.95; T vs. C: OR=1.31, 95% CI: 1.02-1.69) without significant heterogeneity. We conclude that the C677T MTHFR polymorphism, responsible for a reduction of the MTHFR activity in folate metabolism, may act as a genetic susceptibility factor for migraine, MA in particular among the subjects of Asian descent.

Keywords: C677T polymorphism; MTHFR; Meta-analysis; Migraine with aura; Migraine without aura.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics
  • Case-Control Studies
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Migraine Disorders / diagnosis*
  • Migraine Disorders / genetics*
  • Polymorphism, Genetic / genetics*
  • Risk Factors


  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)