The Effect of the MTHFR C677T Single Nucleotide Polymorphism on Plasma Homocysteine Lowering Therapy with Vitamins in the Ischemic Stroke Patients

ABSTRACT

BACKGROUND: C677T single nucleotide polymorphism (SNP) of Methylentetrahydrofolate reductase (MTHFR) has been known to be associated with plasma homocysteine (Hcy) levels, which is an independent risk factor for stroke. However, recent large clinical trials did not show any benefits of Hcy lowering therapy with vitamins on the prevention of stroke. We hypothesized that the Hcy lowering effect by vitamins would be different according to the MTHFR C677T SNP types (CC, CT or TT), which may influence the benefits of vitamins by Hcy lowering on stroke prevention. METHODS: The authors retrospectively studied acute stroke patients with information of the genotype of MTHFR and serial levels of Hcy during a recent 4 year period (July 2002 - Dec 2005). Vitamins (folic acid 1 mg, and/or cobalamin 750 microgram and pyridoxine 75 mg) were prescribed to the patients whose basal plasma Hcy levels were above 12 umol/L. RESULTS: Among 172 patients, 68 patients took vitamins. The mean basal Hcy level was significantly higher in the TT type than the others, and was decreased by vitamin therapy. Distribution of homocysteine grading (normal, intermediate or high) in follow up was not significantly different according to these SNP types. CONCLUSIONS: The Hcy lowering effect by vitamins was not different by MTHFR genetic polymorphism. Considering the higher prevalence of certain gene types in stroke and our study results, genetic factors such as MTHFR polymorphism may play an important role on the development of stroke rather than the plasma Hcy levels.