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.
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. MTHFRC677T genetic variant contributes to simvastatin's effects among Chinese subjects with primary hyperlipidemia.
Authors: Annelies C Ham; Anke W Enneman; Suzanne C van Dijk; Sadaf Oliai Araghi; Karin M A Swart; Evelien Sohl; Janneke P van Wijngaarden; Nikita L van der Zwaluw; Elske M Brouwer-Brolsma; Rosalie A M Dhonukshe-Rutten; Natasja M van Schoor; Tischa J M van der Cammen; M Carola Zillikens; Robert de Jonge; Paul Lips; Lisette C P G M de Groot; Joyce B J van Meurs; André G Uitterlinden; Renger F Witkamp; Bruno H C Stricker; Nathalie van der Velde Journal: Drugs Aging Date: 2014-08 Impact factor: 3.923