A Potential Epigenetic Marker Mediating Serum Folate and Vitamin B₁₂Levels Contributes to the Risk of Ischemic Stroke

Stroke is a multifactorial disease that may be associated with aberrant DNA methylation profiles. We investigated epigenetic dysregulation for the methylenetetrahydrofolate reductase (<i>MTHFR</i>) gene among ischemic stroke patients. Cases and controls were recruited after obtaining signed written informed consents following a screening process against the inclusion/exclusion criteria. Serum vitamin profiles (folate, vitamin B₁₂, and homocysteine) were determined using immunoassays. Methylation profiles for CpGs A and B in the <i>MTHFR</i> gene were determined using a bisulfite-pyrosequencing method. Methylation of <i>MTHFR</i> significantly increased the susceptibility risk for ischemic stroke. In particular, CpG A outperformed CpG B in mediating serum folate and vitamin B₁₂levels to increase ischemic stroke susceptibility risks by 4.73-fold. However, both CpGs A and B were not associated with serum homocysteine levels or ischemic stroke severity. CpG A is a potential epigenetic marker in mediating serum folate and vitamin B₁₂to contribute to ischemic stroke.