Effect of Simvastatin on Plasma Homocysteine Levels and Its Modification by MTHFR C677T Polymorphism in Chinese Patients with Primary Hyperlipidemia

OBJECTIVE: We investigate the effect of simvastatin on plasma homocysteine (Hcy) levels and whether genetic factor affects the effect of simvastatin. METHODS: A total of 338 patients with hyperlipidemia were enrolled. Simvastatin was orally administered at a dose of 20 mg/day for 8 weeks. Plasma Hcy levels were measured by high-performance liquid chromatography at baseline and after 8 weeks of treatment. Genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism was performed by TaqMan probe technique. RESULTS: Serum total Hcy levels were positively correlated with serum creatinine (r = 0.332, P < 0.001). Among total subjects, simvastatin treatment resulted in a significant reduction in serum Hcy levels after 8 weeks (-0.37 ± 2.21 μmol/L, P = 0.003), and this effect was dependent on the initial levels of serum Hcy. The individuals with 677TT genotype had a significantly higher baseline Hcy level and a greater change in Hcy levels. After stratification by body mass index (BMI), we observed a significant increase in Hcy levels among the TT genotype group in adjusted model (beta±SE: 2.64 ± 0.84 μmol/L; P = 0.002) among patients with BMI ≥ 25 (kg/m(2) ). CONCLUSIONS: Simvastatin can cause a marked decrease in plasma Hcy levels. MTHFR C677T genetic variant contributes to simvastatin's effects among Chinese subjects with primary hyperlipidemia.