Wei Loo Keat, Sutherland Heidi, Au Anthony, Camilleri Emily, Haupt Larisa M, Gan Siew Hua, Griffiths Lyn R
Centre for Biodiversity Research, Universiti Tunku Abdul Rahman, Bandar Barat, 31900 Kampar, Perak, Malaysia ; Department of Biological Science, Faculty of Science, Universiti Tunku Abdul Rahman, Bandar Barat, 31900 Kampar, Perak, Malaysia ; Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Musk Avenue, Kelvin Grove, QLD 4059, Australia ; Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Musk Avenue, Kelvin Grove, QLD 4059, Australia.
Biomed Res Int. 2015;2015:167976. doi: 10.1155/2015/167976. Epub 2015 Feb 1.
Stroke is a multifactorial disease that may be associated with aberrant DNA methylation profiles. We investigated epigenetic dysregulation for the methylenetetrahydrofolate reductase (MTHFR) 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 MTHFR gene were determined using a bisulfite-pyrosequencing method. Methylation of MTHFR significantly increased the susceptibility risk for ischemic stroke. In particular, CpG A outperformed CpG B in mediating serum folate and vitamin B12 levels 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 B12 to contribute to ischemic stroke.
中风是一种多因素疾病，可能与异常的DNA甲基化谱有关。我们研究了缺血性中风患者中亚甲基四氢叶酸还原酶（MTHFR）基因的表观遗传失调情况。在根据纳入/排除标准进行筛选后，获得签署的书面知情同意书后招募病例和对照。使用免疫测定法测定血清维生素谱（叶酸、维生素B12和同型半胱氨酸）。使用亚硫酸氢盐焦磷酸测序法测定MTHFR基因中CpG A和B的甲基化谱。MTHFR的甲基化显著增加了缺血性中风的易感性风险。特别是，CpG A在介导血清叶酸和维生素B12水平以将缺血性中风易感性风险提高4.73倍方面比CpG B表现更好。然而，CpG A和B均与血清同型半胱氨酸水平或缺血性中风严重程度无关。CpG A是介导血清叶酸和维生素B12导致缺血性中风的潜在表观遗传标志物。
