Association between Migraine with Aura and both Homocysteine and MTHFR C677T Polymorphism

ABSTRACT

BACKGROUND: The pathophysiology of migraine is not yet fully understood. Homocysteine acts as an excitatory amino acid in vivo and may influence the threshold of migraine. The previous studies have revealed strong association between the homozygous C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and hyperhomocysteinemia. In this study, we examined the association between both homocysteine and MTHFR C677T polymorphism and headache, such as migraine and tension headache. METHODS: We enrolled 148 headache patients (75 tension headache, 34 migraine with aura [MWA], and 39 migraine without aura [MOA]) and 121 normal controls; checked their fasting homocysteine levels and analyzed for the MTHFR C677T polymorphism. For the multivariate analysis, we used logistic regression to adjust for age and sex. RESULTS: Plasma homocysteine levels were significantly higher in patients with MWA than those in controls (adjusted odds ratio (AOR), 1.12; 95% confidence intervals (CI), 1.02~1.23). The AOR and 95% CI of the MTHFR 677TT genotype was significantly higher in patients with total migraine (AOR, 3.32; 95% CI, 1.30~9.55; p< 0.05) and with MWA (AOR, 4.70; 95% CI, 1.44~15.29; p<0.01) than the controls. However, the AOR was not significant in patients with tension headache (AOR, 0.93; 95% CI, 0.37~2.32) and with MOA (AOR, 2.77; 95% CI, 0.78~9.74). CONCLUSIONS: Our findings suggest that both elevated homocysteine level and the homozygous C677T mutation in the MTHFR gene are associated with migraine with aura.