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Background and Objective  Conflicting data have been reported on the association between tumor necrosis factor ( TNF ) –308G>A and nitric oxide synthase 3 ( NOS3 ) +894G>T polymorphisms and migraine. We performed a meta-analysis of case-control studies to evaluate whether the  TNF  –308G>A and  NOS3  +894G>T polymorphisms confer genetic susceptibility to migraine.    Method  We performed an updated meta-analysis for  TNF  –308G>A and a meta-analysis for  NOS3  +894G>T based on studies published up to July 2014. We calculated study specific odds ratios (OR) and 95% confidence intervals (95% CI) assuming allele contrast, dominant model, recessive model, and co-dominant model as pooled effect estimates.    Results  Eleven studies in 6682 migraineurs and 22591 controls for  TNF  –308G>A and six studies in 1055 migraineurs and 877 controls for  NOS3  +894G>T were included in the analysis. Neither indicated overall associations between gene polymorphisms and migraine risk. Subgroup analyses suggested that the “A” allele of the  TNF  –308G>A variant increases the risk of migraine among non-Caucasians (dominant model: pooled OR = 1.82; 95% CI 1.15 – 2.87). The risk of migraine with aura (MA) was increased among both Caucasians and non-Caucasians. Subgroup analyses suggested that the “T” allele of the  NOS3  +894G>T variant increases the risk of migraine among non-Caucasians (co-dominant model: pooled OR = 2.10; 95% CI 1.14 – 3.88).    Conclusions  Our findings appear to support the hypothesis that the  TNF  –308G>A polymorphism may act as a genetic susceptibility factor for migraine among non-Caucasians and that the  NOS3  +894G>T polymorphism may modulate the risk of migraine among non-Caucasians.

Tumor Necrosis Factor (TNF) –308G>A, Nitric Oxide Synthase 3 (NOS3) +894G>T Polymorphisms and Migraine Risk: A Meta-Analysis