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Association of the C677T polymorphism in the MTHFR gene with migraine: a meta-analysis

E Rubino1, M Ferrero, I Rainero

  • 1Neurology II, Headache Centre, Department of Neuroscience, University of Torino, Torino, Italy.

Cephalalgia : an International Journal of Headache
|August 24, 2007
PubMed

Insights

The methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism is linked to migraine with aura. This meta-analysis found the TT genotype increases migraine with aura risk compared to the CC genotype.

Area of Science:

  • Genetics
  • Neurology
  • Molecular Biology

Background:

  • Conflicting data exist regarding the association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and migraine.
  • The C677T polymorphism is known to reduce MTHFR enzyme activity by 50%, potentially leading to hyperhomocysteinemia.

Purpose of the Study:

  • To conduct a meta-analysis of published studies to investigate the association between the MTHFR gene C677T polymorphism and migraine.
  • To determine if specific MTHFR genotypes are associated with an increased risk of migraine or its subtypes.

Main Methods:

  • A meta-analysis was performed on all available studies examining the MTHFR gene and migraine.
  • Pooled odds ratios (OR) were calculated using both random (RE) and fixed effects (FE) models.
  • The analysis included a total of 2961 individuals diagnosed with migraine.

Main Results:

  • No significant association was found between the MTHFR C677T polymorphism and migraine overall when comparing migraineurs to controls.
  • However, in the subgroup of migraine with aura, the TT genotype showed a significantly higher risk compared to the CC genotype (FE OR 1.30, 95% CI 1.06-1.58; RE OR 1.66, 95% CI 1.06-2.59).
  • Further analysis in the migraine with aura subgroup revealed a significant association when comparing the TT genotype to the CT + CC genotypes (FE OR 1.32, 95% CI 1.10-1.59; RE OR 1.63, 95% CI 1.10-2.43).

Conclusions:

  • This meta-analysis provides evidence suggesting a specific association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and migraine with aura.
  • The TT genotype of the MTHFR C677T polymorphism appears to be a risk factor for developing migraine with aura.

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