Migraine Mediates the Influence of C677T MTHFR Genotypes on Ischemic Stroke Risk With a Stroke-Subtype Effect
- 1 December 2007
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Stroke
- Vol. 38 (12), 3145-3151
- https://doi.org/10.1161/strokeaha.107.491506
Abstract
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.This publication has 27 references indexed in Scilit:
- Testing of Variants of theMTHFRandESR1Genes in 1798 Finnish Individuals Fails to Confirm the Association with Migraine with AuraCephalalgia, 2006
- Migraine and MTHFR C677T genotype in a population‐based sampleAnnals of Neurology, 2005
- History of Migraine and the Risk of Spontaneous Cervical Artery DissectionCephalalgia, 2005
- Homocysteine and stroke: evidence on a causal link from mendelian randomisationThe Lancet, 2005
- Clinical Benefits of Early Triptan Therapy for MigraineCephalalgia, 2004
- Statistical assessment of mediational effects for logistic mediational modelsStatistics in Medicine, 2004
- Hyperhomocysteinemia, Oxidative Stress, and Cerebral Vascular DysfunctionStroke, 2004
- How Do Risk Factors Work Together? Mediators, Moderators, and Independent, Overlapping, and Proxy Risk FactorsAmerican Journal of Psychiatry, 2001
- A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductaseNature Genetics, 1995
- The moderator–mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations.Journal of Personality and Social Psychology, 1986