Objective
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.
Background
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.
Methods
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.
Results
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: X2 = 0.18 [P = .91]; ACE: X2 = 1.62 [P = .45]; combined: OR = 1.02 [95% CI 0.98‐1.05] P = .97).
Conclusions
We could not replicate a previous study that showed significant increase in migraine susceptibility for two functional polymorphisms in genes affecting relevant pathways.