Effect of simvastatin on plasma homocysteine levels and its modification by MTHFR C677T polymorphism in Chinese patients with primary hyperlipidemia

Cardiovasc Ther. 2013 Aug;31(4):e27-33. doi: 10.1111/1755-5922.12002.

Abstract

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.

Keywords: Homocysteine; MTHFR C677T; Polymorphism; Primary hyperlipidemia; Simvastatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Asian People / genetics
  • Biomarkers / blood
  • Chi-Square Distribution
  • China / epidemiology
  • Chromatography, High Pressure Liquid
  • Down-Regulation
  • Female
  • Homocysteine / blood*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hyperlipidemias / blood
  • Hyperlipidemias / drug therapy*
  • Hyperlipidemias / enzymology
  • Hyperlipidemias / ethnology
  • Hyperlipidemias / genetics
  • Linear Models
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Multivariate Analysis
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Simvastatin / administration & dosage
  • Simvastatin / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Homocysteine
  • Simvastatin
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)