title: Migraine mediates the influence of C677T MTHFR genotypes on ischemic stroke risk with a stroke-subtype effect.
abstract: OBJECTIVE
  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.
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche, Stroke Unit, Neurologia Vascolare, Spedali Civili di Brescia, P. le Spedali Civili, 1, 25100 Brescia, Italia. ale_pezzini@hotmail.com
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pezzini
authors.forename: Mario
authors.initials: M
authors.lastname: Grassi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Del Zotto
authors.forename: Alessia
authors.initials: A
authors.lastname: Giossi
authors.forename: Roberto
authors.initials: R
authors.lastname: Monastero
authors.forename: Giorgio
authors.initials: G
authors.lastname: Dalla Volta
authors.forename: Silvana
authors.initials: S
authors.lastname: Archetti
authors.forename: Paola
authors.initials: P
authors.lastname: Zavarise
authors.forename: Cecilia
authors.initials: C
authors.lastname: Camarda
authors.forename: Roberto
authors.initials: R
authors.lastname: Gasparotti
authors.forename: Mauro
authors.initials: M
authors.lastname: Magoni
authors.forename: Rosolino
authors.initials: R
authors.lastname: Camarda
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
mesh_terms: D000328:Adult; D001808:Blood Vessels / Q000473:pathology*; D046589:CADASIL / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D008881:Migraine Disorders / Q000150:complications / Q000175:diagnosis*; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D012306:Risk; D012307:Risk Factors; D020521:Stroke / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)