title: Methylenetetrahydrofolate reductase polymorphisms and homocysteine-lowering effect of vitamin therapy in Singaporean stroke patients.
abstract: OBJECTIVE
  Increased plasma total homocysteine (tHcy) levels are a risk factor for stroke and can be reduced with vitamin therapy. However, data on the tHcy-lowering effects of vitamins are limited largely to white populations. Thus, we aimed to determine in Singaporean patients with recent stroke: (1) the efficacy of vitamin therapy (folic acid, vitamin B12, and B6) on lowering tHcy, and (2) whether efficacy is modified by Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism(s).
  
  
  METHODS
  A total of 443 eligible patients were recruited after presenting with ischemic stroke within the past 7 months. Patients were randomized to receive either placebo or vitamins. Fasting blood samples collected at baseline and at 1 year were assayed for levels of plasma tHcy. Patients were genotyped for MTHFR C677T and A1298C polymorphisms.
  
  
  RESULTS
  Mean baseline tHcy was similar in the 2 groups (placebo 13.7 micromol/L; vitamins 14.0 micromol/L; P=0.70). At 1 year, mean tHcy was 14.5 micromol/L in the placebo group compared with 10.7 micromol/L in the vitamin group (difference 3.8 micromol/L; 95% CI, 2.8 to 4.8 micromol/L; P<0.0001). MTHFR C677T genotype was an independent determinant of tHcy levels at baseline (P=0.005), but A1298C was not (P=0.08). Neither polymorphism significantly influenced the effect of vitamin therapy on tHcy at 1 year. The magnitude of the reduction in tHcy levels at 1 year with vitamin therapy was similar, irrespective of MTHFR genotypes.
  
  
  CONCLUSIONS
  Vitamin therapy reduces mean tHcy levels by 3.8 micromol/L in the Singaporean stroke population studied. MTHFR C677T but not A1298C is independently associated with tHcy levels at baseline, and neither impacts the tHcy-lowering effect of vitamins used in this study.
authors.affiliation: Department of Neurology, Singapore General Hospital, Singapore.
authors.forename: Grace Y-H
authors.initials: GY
authors.lastname: Ho
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: Chen-Ru
authors.initials: CR
authors.lastname: Wong
authors.forename: Siew-Li
authors.initials: SL
authors.lastname: Tan
authors.forename: Jesscia B-C
authors.initials: JB
authors.lastname: Chan
authors.forename: Christopher P L-H
authors.initials: CP
authors.lastname: Chen
mesh_terms: D000368:Aged; D003324:Coronary Artery Disease / Q000517:prevention & control* / Q000628:therapy; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000628:therapy*; D002546:Ischemic Attack, Transient / Q000208:ethnology / Q000235:genetics* / Q000628:therapy; D008297:Male; D045102:Methylenetetrahydrofolate Dehydrogenase (NAD+) / Q000235:genetics*; D008875:Middle Aged; D015233:Models, Statistical; D010919:Placebos; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012307:Risk Factors; D012846:Singapore; D020521:Stroke / Q000208:ethnology / Q000235:genetics* / Q000628:therapy; D014805:Vitamin B 12 / Q000627:therapeutic use; D025101:Vitamin B 6 / Q000627:therapeutic use; D014815:Vitamins / Q000378:metabolism*
chemical_list: D010919:Placebos; D014815:Vitamins; D006710:Homocysteine; D025101:Vitamin B 6; D005492:Folic Acid; D045102:Methylenetetrahydrofolate Dehydrogenase (NAD+); D014805:Vitamin B 12