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 I2. 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.