title: A potential epigenetic marker mediating serum folate and vitamin B12 levels contributes to the risk of ischemic stroke.
abstract: 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.
authors.affiliation: 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.
authors.forename: Loo Keat
authors.initials: LK
authors.lastname: Wei
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Musk Avenue, Kelvin Grove, QLD 4059, Australia.
authors.forename: Heidi
authors.initials: H
authors.lastname: Sutherland
authors.affiliation: Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Au
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Musk Avenue, Kelvin Grove, QLD 4059, Australia.
authors.forename: Emily
authors.initials: E
authors.lastname: Camilleri
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Musk Avenue, Kelvin Grove, QLD 4059, Australia.
authors.forename: Larisa M
authors.initials: LM
authors.lastname: Haupt
authors.affiliation: Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
authors.forename: Siew Hua
authors.initials: SH
authors.lastname: Gan
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Musk Avenue, Kelvin Grove, QLD 4059, Australia.
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
mesh_terms: D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D012306:Risk; D020521:Stroke / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D014805:Vitamin B 12 / Q000097:blood*
chemical_list: D005819:Genetic Markers; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12