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(Stroke. 2006;37:456.)
© 2006 American Heart Association, Inc.

Original Contributions

Methylenetetrahydrofolate Reductase Polymorphisms and Homocysteine-Lowering Effect of Vitamin Therapy in Singaporean Stroke Patients

Grace Y.-H. Ho, BSc (Hons); John W. Eikelboom, FRCPA; Graeme J. Hankey, FRACP; Chen-Ru Wong, BSc; Siew-Li Tan, BSc; Jesscia B.-C. Chan, BSc Christopher P.L.-H. Chen, FRCP

From the Department of Neurology (G.Y.-H.H., C.-R.W., S.-L.T.), Singapore General Hospital; Department of Medicine (J.W.E.), McMaster University, Hamilton, Canada; Stroke Unit (G.J.H.), Royal Perth Hospital, Australia; and Department of Neurology (J.B.-C.C., C.P.L.-H.), National Neuroscience Institute, Singapore General Hospital Campus.

Correspondence to Christopher P.L.-H. Chen, Department of Neurology, Block-6, Level-8, Singapore General Hospital, Outram Road, Singapore 169608. E-mail gnrcc{at}sgh.com.sg

Background and Purpose— 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 µmol/L; vitamins 14.0 µmol/L; P=0.70). At 1 year, mean tHcy was 14.5 µmol/L in the placebo group compared with 10.7 µmol/L in the vitamin group (difference 3.8 µmol/L; 95% CI, 2.8 to 4.8 µmol/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 µmol/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.

Key Words: methylenetetrahydrofolate reductase • polymorphism • homocysteine • stroke

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Homocysteine: Call Off the Funeral

J. David Spence
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