Hyperhomocysteinemia and Methylenetetrahydrofolate Reductase Polymorphism in Cervical Artery Dissection: A Meta-Analysis

Abstract

Background: Cervical artery dissection (CAD) is a recognized cause of ischemic stroke. Hyperhomocysteinemia (HHcy), i.e. an elevated concentration of plasma homocysteine, is identified as an independent risk factor for stroke prevalence. However, an association between HHcy and CAD has so far remained unknown. Methods: A meta-analysis was performed to analyze the association between HHcy and CAD as well as the relevance of the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR), the key enzyme in homocysteine metabolism during CAD. We searched PubMed and Embase for studies reporting homocysteine concentrations or MTHFR genotype frequencies in CAD patients from 1990 to 2013. Outcomes were extracted from studies meeting the inclusion criteria and were subjected to a meta-analysis by the random-effect model. Heterogeneity was assessed by the I² test. Results: Eight case-control studies with 2,146 individuals fulfilled the required criteria and were included in the meta-analysis. HHcy was found to be significantly associated with CAD (pooled standardized mean difference: 0.96; 95% confidence interval, CI: 0.42-1.49; p < 0.01). We also found a significantly increased risk of CAD in individuals with the MTHFR C677T polymorphism by both the recessive model (TT vs. CT+CC; odds ratio, OR = 1.81; 95% CI: 1.22-2.67; p = 0.003) and the dominant model (TT+CT vs. CC; OR = 1.47; 95% CI: 1.08-1.99; p = 0.014). Conclusion: Our data suggest positive correlations between HHcy and CAD and between the C677T polymorphism of MTHFR and CAD.

Hyperhomocysteinaemia and vascular injury: advances in mechanisms and drug targets

“…The polymorphisms MTHFR C677T, MTHFR A1298C and MS A2756G, are the critical dominant negative mutations and they jointly add to the risk of folate deficiency, which results in HHcy in humans (Li et al ., ). The MTHFR C677T polymorphism has been identified as a risk locus in patients with coronary heart disease, coronary artery calcification, cervical artery dissection, aortic aneurysm and dissection (Fallon and Ben‐Shlomo, ; Takagi and Umemoto, ; Holmes et al ., ; Clarke et al ., ; Liu et al ., ; Luo et al ., ; Kim et al ., ; Wang et al ., ). To further assess the causality of this single‐nucleotide polymorphism in HHcy‐related vascular injury and disease, Mendelian randomization studies have been carried out by several groups.…”

“…To date, a substantial amount of data from case–control cohort studies and meta‐analyses support the association of HHcy with a range of vascular diseases, including hypertension, ischaemic stroke, aortic aneurysm and dissection, coronary heart disease, coronary artery calcification, vascular dementia and cervical artery dissection. as HHcy has also been identified as a risk factor for these diseases (Fallon and Ben‐Shlomo, ; Ravaglia et al ., ; Takagi and Umemoto, ; Holmes et al ., ; Clarke et al ., ; Liu et al ., , ; Luo et al ., ; Kim et al ., ; Wang et al ., ).…”

The Link Between Migraine, Reversible Cerebral Vasoconstriction Syndrome and Cervical Artery Dissection

“…Another hypothesis to explain the increased risk of CeAD among migraineurs relies on the MTHFR gene polymorphism, which plays a role in homocysteine metabolism and may be involved in endothelial dysfunction . However, although candidate gene association studies suggested an association of the MTHFR 677CT polymorphism with the risk of CeAD and migraine, recent genome‐wide association studies of CeAD and migraine on much larger samples did not confirm this association.…”

Bilateral internal carotid artery dissection associated with prior syphilis: a case report and review of the literature

“…3 A mild hyperhomocysteinemia, as detected in our patient, could be considered as a risk factor by means of damage to arterial wall. 4 Among the other typical risk factors for cervical artery dissection, there was no history of head or cervical trauma in the recent past. 5 Moreover, there was no previous or active drug abuse.…”