Association of the A1298C polymorphism in MTHFR gene with ischemic stroke

A meta-analysis was performed to assess the association between the methylenetetrahydrofolate reductase (MTHFR) A1298C genetic polymorphism and ischemic stroke. A comprehensive search was conducted to identify all case-control or cohort studies. The fixed or random effect pooled measure was selected based on the homogeneity between studies, as assessed by I(2). Meta-regression was used to explore the potential sources of between-study heterogeneity. Publication bias was estimated using Egger's linear regression test. Thirteen case-control studies corresponded to the inclusion criteria comprising 2133 patients and 2572 controls which were included in the present meta-analysis. After excluding articles that deviated from Hardy-Weinberg equilibrium in controls and the key contributors to between-study heterogeneity, significant associations between MTHFR A1298C genetic polymorphism and risk of ischemic stroke were observed in dominant (odds ratio [OR] 1.227, 95% confidence interval [CI] 1.062-1.416) and codominant (OR 1.138, 95% CI 1.007-1.286) inheritance models. Moreover, in the subgroup analysis based on region (Asia and Europe), significant associations were observed in most genetic models in Asia but not in Europe. This meta-analysis suggests that MTHFR A1298C genetic polymorphism is associated with increased risk of ischemic stroke, and the C allele may be an important risk factor for ischemic stroke.