Published Online
on October 25, 2007

A more recent version of this article appeared on December 1, 2007

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Submitted on April 17, 2007
Revised on May 17, 2007
Accepted on May 30, 2007

Migraine Mediates the Influence of C677T MTHFR Genotypes on Ischemic Stroke Risk With a Stroke-Subtype Effect

Alessandro Pezzini MD^*; Mario Grassi PhD; Elisabetta Del Zotto MD; Alessia Giossi MD; Roberto Monastero MD, PhD; Giorgio Dalla Volta MD; Silvana Archetti MD; Paola Zavarise MD; Cecilia Camarda MD; Roberto Gasparotti MD; Mauro Magoni MD; Rosolino Camarda MD; and Alessandro Padovani MD, PhD

From Dipartimento di Scienze Mediche e Chirurgiche (A.P., M.M.), Stroke Unit, Neurologia Vascolare, Spedali Civili di Brescia, Brescia, Italia; Dipartimento di Scienze Sanitarie Applicate (M.G.), Sezione di Statistica Medica e Epidemiologia, Università di Pavia, Pavia, Italia; Dipartimento di Scienze Mediche e Chirurgiche (E.D.Z., A.G., A.P.), Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia; Dipartimento di Neuroscienze Cliniche (R.M., C.C., R.C.), Divisione di Neurologia e Riabilitazione Neurologica, Università degli Studi di Palermo, Palermo, Italia; Unità Operativa di Neurologia (G.D.V., P.Z.), Centro Cefalee, Istituto Clinico Città di Brescia, Brescia, Italia; III Laboratorio di Analisi (S.A.), Biotecnologie, Università degli Studi di Brescia, Brescia, Italia; Dipartimento di Diagnostica per Immagini (R.G.), Neuroradiologia, Università degli Studi di Brescia, Brescia, Italia.

^* To whom correspondence should be addressed. E-mail: ale_pezzini{at}hotmail.com.

Background and Purpose—The objective was to investigate the role of C677T MTHFR polymorphism in migraine pathogenesis and in the migraine–ischemic stroke pathway.

Methods—A first genotype–migraine association study was conducted on 100 patients with migraine with aura (MA), 106 with migraine without aura (MO), and 105 subjects without migraine, which provided evidence in favor of association of the TT677 MTHFR genotype with increased risk of MA compared with both control subjects (OR, 2.48; 95% CI, 1.11 to 5.58) and patients with MO (OR, 2.21; 95% CI, 1.01 to 4.82). Based on these findings, mediational models of the genotype–migraine–stroke pathway were fitted on a group of 106 patients with spontaneous cervical artery dissection, 227 young patients whose ischemic stroke was unrelated to a spontaneous cervical artery dissection (noncervical artery dissection), and 187 control subjects, and a genotype–migraine partial mediation model was selected.

Results—Both migraine and the TT genotype were more strongly associated to the subgroup of patients with spontaneous cervical artery dissection (OR, 4.06; 95% CI, 1.63 to 10.02 for MA; OR, 5.45; 95% CI, 3.03 to 9.79 for MO; OR, 2.87; 95% CI, 1.45 to 5.68 for TT genotype) than to the subgroup of patients with noncervical artery dissection ischemic stroke (OR, 2.22; 95% CI, 1.00 to 4.96 for MA; OR, 1.81; 95% CI, 1.02 to 3.22 for TT genotype) as compared with controls.

Conclusions—Migraine may act as mediator in the methylenetetrahydrofolate reductase–ischemic stroke pathway with a more prominent effect in the subgroup of patients with spontaneous artery dissection.

Key words: genetics • migraine • risk factors • stroke in young adults

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Blood Vessels, Migraine, and Stroke

Michael A. Moskowitz and Tobias Kurth
Stroke 2007 38: 3117-3118. [Extract] [Full Text] [PDF]

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