Hyperhomocysteinemia and methylenetetrahydrofolate reductase polymorphism in cervical artery dissection: a meta-analysis

Cerebrovasc Dis. 2014;37(5):313-22. doi: 10.1159/000360753. Epub 2014 Jun 4.

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 I(2) 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arteries / physiopathology*
  • Case-Control Studies
  • Coronary Artery Disease / complications
  • Genetic Predisposition to Disease*
  • Genotype*
  • Humans
  • Hyperhomocysteinemia / complications
  • Hyperhomocysteinemia / diagnosis*
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Neck
  • Odds Ratio
  • Polymorphism, Genetic / genetics*
  • Risk

Substances

  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)

Supplementary concepts

  • Homocysteinemia