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

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 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.