MTHFR and ACE Polymorphisms Do Not Increase Susceptibility to Migraine Neither Alone Nor in Combination

The aim of this study was to confirm previous reports in order to substantiate the hypothesis that functional variants of two genes, namely methylenetetrahydrofolate reductase and angiotensin I converting enzyme, both involved in an important pathway of migraine, increase migraine susceptibility when present in combination.

Migraine is a complex genetic disease. The migraine attack is thought to be the result of an interaction of neuronal and vascular events, possibly originating in the brainstem leading to activation of the pain processing trigeminovascular system. Functional variants in the methylenetetrahydrofolate gene and the angiotensin I converting enzyme have influence on vascular mechanism and have been investigated intensively in migraine. The published results were inconsistent; however, both polymorphisms in combination have been shown to increase migraine susceptibility.

In this genetic association study, the prevalence of the functionally relevant polymorphisms C677T in the MTHFR gene and I/D polymorphism in the ACE gene was compared in 420 patients with migraine vs 258 migraine-free controls using a chi-square statistic and binary logistic regression.

Susceptibility to any type of migraine (migraine with aura, migraine without aura, and both types combined) was neither increased by each polymorphism on its own, nor in combination (MTHFR: X(2)  = 0.18 [P = .91]; ACE: X(2)  = 1.62 [P = .45]; combined: OR = 1.02 [95% CI 0.98-1.05] P = .97).

We could not replicate a previous study that showed significant increase in migraine susceptibility for two functional polymorphisms in genes affecting relevant pathways.