Tumour necrosis factor gene polymorphisms and migraine: A systematic review and meta-analysis

Background: Data on the association between TNF alpha and TNF beta gene polymorphisms and migraine are conflicting. Methods: We performed a systematic review and meta-analysis of studies published until January 2011. We used data from published papers and as provided after contact with the authors. We calculated study specific odds ratios (OR) and 95% confidence intervals (CI) assuming additive, dominant, and recessive genetic models as well as pooled effect estimates. Results: Among the ten studies identified, the best evidence is available for the TNF alpha -308G > A and TNF beta 252A > G polymorphisms indicating no overall association with migraine. Subgroup analyses suggested that the A allele of the TNF alpha -308G > A variant more than doubles the risk for migraine among populations with a heterogeneous ethnic background, which was driven by associations for migraine without aura (additive model: pooled OR = 2.87, 95% CI 1.86-4.43). Further, the risk for migraine with aura was increased among Asian populations (additive model: pooled OR = 1.71, 95% CI 1.07-2.71). Both observed effects were stronger among females than males. Conclusions: Our results indicate no overall association between TNF alpha and TNF beta gene variants and migraine. However, associations differed among specific populations. Our findings need to be treated with caution and further targeted research is warranted to evaluate population-specific effects including population stratification.