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 20mg/day for 8weeks. Plasma Hcy levels were measured by high-performance liquid chromatography at baseline and after 8weeks 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 8weeks (-0.37 +/- 2.21mol/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 +/- 0.84mol/L; P=0.002) among patients with BMI25 (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.