A potential epigenetic marker mediating serum folate and vitamin B12 levels contributes to ischemic stroke risk

摘要

Background and PurposeududStroke is a multifactorial disease that may be associated with aberrant DNA methylation profiles.We investigated epigenetic dysregulation for the MTHFR gene among ischaemic stroke patients.ududMethodsududCases (n=297) and controls (n=110) were recruited after obtaining signed written informed consent, following a screening process against the inclusion/exclusion criteria. Serum vitamin metabolites (folate, vitamin B12 and homocysteine) were determined using immunoassays and methylation profiles for CpGs A and B in the MTHFR gene were determined using bisulfitepyrosequencingudmethod.ududResultsududMethylation of MTHFR significantly increased the susceptibility risk for ischemic stroke. In particular, CpG A outperformed CpG B in mediating folate and vitamin B12 levels to increase ischemic stroke susceptibility risks by 4.73 fold. CpGs A and B were not associated with eitherudserum homocysteine levels or ischemic stroke severity.ududConclusionududCpG A is a potential epigenetic marker in mediating serum folate and vitamin B12 to contribute to ischemic stroke.