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Migraine with Aura, Gene Polymorphisms, and Stroke Risk

In this analysis from the Women’s Health Study, the twofold increased risk for stroke associated with migraine with aura was increased to four-fold in patients with a common polymorphism of the MTHFR gene.

The aim of this study was to explore associations among a common polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, migraine, and cardiovascular disease (CVD; stroke and myocardial infarction [MI]). Some 25,000 participants in the Women’s Health Study provided blood samples and epidemiologic data. Participants were classified according to self-report at baseline as having migraine with aura (MWA; report of "aura or any indication a migraine is coming") or migraine without aura. Cardiovascular events during a mean 12 years of follow-up were self-reported and confirmed by chart review.

In an analysis adjusted for other CVD risk factors, active MWA increased the risk for CVD (both ischemic stroke and MI) approximately twofold compared with no migraine. Patients with both MWA and the TT genotype of the MTHFR gene had an even higher risk for ischemic stroke (approximately fourfold), but not for MI, compared with women without migraine and with the CC or CT genotype. Carriers of the TT genotype were, however, less likely than were those with the CC or CT genotype to have MWA, and the TT genotype alone did not increase the risk for incident CVD.

Comment: The substantial number of participants and long-term follow-up make this study extremely powerful. However, the value of genetic-association studies depends on the accuracy of the phenotyping. Thus, this study’s major drawback lies in the classification of migraine with aura according to self-report. Some patients without aura but with premonitory symptoms were likely misclassified as having MWA. Nonetheless, the study clearly confirms that certain subgroups of migraine patients (here, those with aura) are prone to CVD and that, among these patients, genetic markers can disclose patients who are at even greater risk. The data offer the beginnings of ways to identify particularly high-risk patients who would benefit from more-aggressive risk-reduction strategies.

— Till Sprenger, MD, and Peter J. Goadsby, MD, PhD

Dr. Sprenger is Clinical Research Fellow, Headache Group, Department of Neurology, University of California, San Francisco. Dr. Goadsby is Director, Headache Group, Department of Neurology, University of California, San Francisco.

Published in Journal Watch Neurology December 9, 2008

Citation(s):

Schürks M et al. Interrelationships among the MTHFR 677C>T polymorphism, migraine, and cardiovascular disease. Neurology 2008 Aug 12; 71:505.

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