Migraine and MTHFR C677T genotype in a population-based sample

Objective: Migraine with aura is associated with increased risk of stroke. The MTHFR C677T genotype has been associated with increased risk of migraine in selected clinical samples and with elevated homocysteine, a risk factor for stroke. We assessed the association of the MTHFR C677T variant with migraine and the mediating effect of cardiovascular risk factors and metabolic markers of genotype status. Methods: We compared adult migraineurs with aura (MA; n = 187), without aura (MO; n = 226), and nonmigraineurs (n = 1,212) from the population-based Genetic Epidemiology of Migraine study. Results: Compared with the wild-type genotype, the T/T genotype was associated with increased odds of MA (odds ratio [OR], 2.05; 95% confidence interval, 1.2-3.4; p < 0.006), with a trend of increasing numbers of T alleles (OR, 1.40; 95% confidence interval, 1.1-1.8; p < 0.007). ORs were slightly attenuated after adjusting for homocysteine. Interpretation: Risk of MA is associated with MTHFR C674T homozygosity, independent of other cardiovascular risk factors.