title: Effect of simvastatin on plasma homocysteine levels and its modification by MTHFR C677T polymorphism in Chinese patients with primary hyperlipidemia.
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.
authors.affiliation: School of Life Sciences, Anhui University, Hefei, China. shanqun@gmail.com
authors.forename: Shanqun
authors.initials: S
authors.lastname: Jiang
authors.forename: Qianru
authors.initials: Q
authors.lastname: Chen
authors.forename: Scott A
authors.initials: SA
authors.lastname: Venners
authors.forename: Guisheng
authors.initials: G
authors.lastname: Zhong
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Hsu
authors.forename: Houxun
authors.initials: H
authors.lastname: Xing
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wang
authors.forename: Xiping
authors.initials: X
authors.lastname: Xu
mesh_terms: D000284:Administration, Oral; D000328:Adult; D044466:Asian People / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D002851:Chromatography, High Pressure Liquid; D015536:Down-Regulation; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000208:ethnology / Q000235:genetics; D016014:Linear Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006710:Homocysteine; D019821:Simvastatin; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Homocysteine; MTHFR C677T; Polymorphism; Primary hyperlipidemia; Simvastatin