Migraine and MTHFR C677T genotype in a population‐based sample

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. 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. 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. Risk of MA is associated with MTHFR C674T homozygosity, independent of other cardiovascular risk factors. Ann Neurol 2006