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Migraine mediates the influence of C677T MTHFR genotypes on ischemic stroke risk with a stroke-subtype effect
Alessandro Pezzini1, Mario Grassi, Elisabetta Del Zotto
1Dipartimento 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
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.
Insights
The C677T MTHFR gene variant is linked to an increased migraine risk, particularly migraine with aura. This genetic factor may mediate the pathway between methylenetetrahydrofolate reductase and ischemic stroke, especially in spontaneous artery dissection cases.
Area of Science:
- Genetics and Neurology
- Cardiovascular Research
Background:
- The methylenetetrahydrofolate reductase (MTHFR) gene, specifically the C677T polymorphism, is investigated for its potential role in neurological conditions.
- Migraine and ischemic stroke are significant health concerns with complex underlying mechanisms.
Purpose of the Study:
- To explore the association between the C677T MTHFR polymorphism and the pathogenesis of migraine.
- To elucidate the role of this polymorphism in the pathway linking migraine to ischemic stroke.
Main Methods:
- A genotype-migraine association study was conducted comparing patients with migraine with aura (MA), migraine without aura (MO), and controls.
- Mediational models were employed to analyze the pathway from MTHFR genotype to migraine and subsequently to ischemic stroke in patients with spontaneous cervical artery dissection and non-dissection ischemic stroke.
Main Results:
- The TT genotype of MTHFR was associated with an increased risk of MA compared to controls and MO patients.
- Migraine and the TT genotype showed a stronger association with spontaneous cervical artery dissection-related ischemic stroke than with non-dissection ischemic stroke.
Conclusions:
- Migraine may function as a mediator in the methylenetetrahydrofolate reductase-ischemic stroke pathway.
- This mediating effect appears more pronounced in individuals experiencing spontaneous artery dissection.
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