title: Clinical Relevance of MTHFR, eNOS, ACE, and ApoE Gene Polymorphisms and Serum Vitamin Profile among Malay Patients with Ischemic Stroke.
abstract: BACKGROUND
  The purpose of this study was threefold. First, it was to determine the relationship between serum vitamin profiles and ischemic stroke. The second purpose was to investigate the association of methylenetetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE), and apolipoprotein-E (ApoE) gene polymorphisms with ischemic stroke and further correlate with serum vitamin profiles among ischemic stroke patients. The third purpose of the study was to highlight the interaction of MTHFR and eNOS haplotypes with serum vitamin profiles and ischemic stroke risks.
  
  
  METHODS
  Polymorphisms of these genes were analyzed in age-, sex-, and ethnicity-matched case-controls (n = 594); serum vitamin profiles were determined using immunoassays.
  
  
  RESULTS
  The MTHFR 677C>T, 1298A>C, eNOS intron 4a/b, and ApoE polymorphisms were significantly associated with the increased risk of ischemic stroke. Elevated serum homocysteine and vitamin B12 levels were associated with MTHFR 677C>T and eNOS intron 4a/b polymorphisms. The ApoE and eNOS -786T>C polymorphisms were associated with increased serum vitamin B12 levels. However, none of the polymorphisms influenced serum folate levels except for the MTHFR 1298A>C. Different patterns of MTHFR and eNOS haplotypes tend to affect serum vitamin profiles to different degrees, which contribute to either different susceptibility risk or protective effect on ischemic stroke. Overall, increased levels of serum homocysteine and vitamin B12 levels were associated with higher risk of ischemic stroke in the investigated population.
  
  
  CONCLUSIONS
  The present study suggests that the genotypes and haplotypes of MTHFR 677C>T and eNOS intron 4a/b polymorphisms are potential serum biomarkers in the pathophysiological processes of ischemic stroke, by modulating homocysteine and vitamin B12 levels.
authors.affiliation: Centre for Biodiversity Research, Universiti Tunku Abdul Rahman, Perak, Malaysia; Department of Biological Science, Faculty of Science, Universiti Tunku Abdul Rahman, Perak, Malaysia; Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia; Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia. Electronic address: wynnelkw@gmail.com.
authors.forename: Loo Keat
authors.initials: LK
authors.lastname: Wei
authors.affiliation: Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 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, Kelvin Grove, Queensland, Australia.
authors.forename: Saras
authors.initials: S
authors.lastname: Menon
authors.affiliation: Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 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, Kelvin Grove, Queensland, Australia.
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
mesh_terms: D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics*; D002545:Brain Ischemia / Q000150:complications; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008296:Malaysia; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020521:Stroke / Q000097:blood* / Q000209:etiology / Q000235:genetics*; D014815:Vitamins / Q000097:blood*
chemical_list: D001057:Apolipoproteins E; D014815:Vitamins; D052250:Nitric Oxide Synthase Type III; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: Gene polymorphisms; folate; homocysteine; stroke; vitamin B(12)