Association of the C677T Polymorphism in the MTHFR Gene with Hemorrhagic Stroke: A Meta-Analysis

Aims: We performed a meta-analysis to assess the possible association between the MTHFR gene C677T polymorphism and hemorrhagic stroke. Methods: A comprehensive search was conducted to identify all case-control or cohort design studies of the associations between C677T and HS. The fixed or random effect pooled measure was selected on the basis of a homogeneity test among studies. Heterogeneity among studies was evaluated using the I-2. Meta-regression and the "leave-one-out" sensitive analysis of Patsopoulos et al. were used to explore potential sources of between-study heterogeneity. Publication bias was estimated using the Begg's test. Results: Fifteen case-control studies corresponded to the inclusion criteria, including 2034 cases and 4485 controls for the present meta-analysis. After excluding articles that deviated from the Hardy-Weinberg equilibrium in controls and the key contributors to between-study heterogeneity, significant associations between the MTHFR C677T genetic polymorphism and the risk of hemorrhagic stroke were observed in dominant (Odds ratio [OR] 1.611, 95% confidence interval [CI] 1.336-1.942), codominant (OR 1.500, 95% CI 1.330-1.692), and recessive (OR 1.695, 95% CI 1.409-2.038) models. Conclusions: The meta-analysis suggests that the MTHFR C667T genetic polymorphism was associated with increased risk of hemorrhagic stroke, and the T allele may be an important risk factor for hemorrhagic stroke. The findings are of importance to the genetic epidemiology of hemorrhagic stroke, and to explore genetic diagnosis, treatment, and prevention of hemorrhagic stroke.