This Article Full Text Full Text (PDF) All Versions of this Article: 38/12/3145    most recent STROKEAHA.107.491506v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pezzini, A. Articles by Padovani, A. Search for Related Content PubMed PubMed Citation Articles by Pezzini, A. Articles by Padovani, A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Genetics Home Reference Medline Plus Health Information Headache Migraine Stroke Related Collections Carotid and Vertebral A. Dissection Genetics of Stroke Risk Factors for Stroke Related Article

(Stroke. 2007;38:3145.)
© 2007 American Heart Association, Inc.

Original Contributions

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 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.

Correspondence to Alessandro Pezzini, Stroke Unit, Neurologia Vascolare, Spedali Civili di Brescia, P. le Spedali Civili, 1, 25100 Brescia, Italia. 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

Related Article:

Blood Vessels, Migraine, and Stroke

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

This article has been cited by other articles:

				A. I. Scher, L. S. Gudmundsson, S. Sigurdsson, A. Ghambaryan, T. Aspelund, G. Eiriksdottir, M. A. van Buchem, V. Gudnason, and L. J. Launer Migraine Headache in Middle Age and Late-Life Brain Infarcts JAMA, June 24, 2009; 301(24): 2563 - 2570. [Abstract] [Full Text] [PDF]

				S. Debette and H. S. Markus The Genetics of Cervical Artery Dissection: A Systematic Review Stroke, June 1, 2009; 40(6): e459 - e466. [Abstract] [Full Text] [PDF]

				M. Schurks, R.Y.L. Zee, J. E. Buring, and T. Kurth ACE D/I polymorphism, migraine, and cardiovascular disease in women Neurology, February 17, 2009; 72(7): 650 - 656. [Abstract] [Full Text] [PDF]

				T. Kurth, C. Tzourio, and M.-G. Bousser Migraine: A Matter of the Heart? Circulation, September 30, 2008; 118(14): 1405 - 1407. [Full Text] [PDF]

				M. Schurks, R. Y.L. Zee, J. E. Buring, and T. Kurth Interrelationships among the MTHFR 677C>T polymorphism, migraine, and cardiovascular disease Neurology, August 12, 2008; 71(7): 505 - 513. [Abstract] [Full Text] [PDF]

				M. A. Moskowitz and T. Kurth Blood Vessels, Migraine, and Stroke Stroke, December 1, 2007; 38(12): 3117 - 3118. [Full Text] [PDF]