title: Effects of atorvastatin and T-786C polymorphism of eNOS gene on plasma metabolic lipid parameters.
abstract: BACKGROUND
  Endothelial nitric oxide synthase (eNOS) activity may be modulated by high-density lipoprotein cholesterol (HDL-C), statins or polymorphisms, such as the T-786C of eNOS.
  
  
  OBJECTIVE
  This study aimed at evaluating if the T-786C polymorphism is associated with changes of atorvastatin effects on the lipid profile, on the concentrations of metabolites of nitric oxide (NO) and of high sensitivity C-reactive protein (hsCRP).
  
  
  METHODS
  Thirty male volunteers, asymptomatic, aged between 18 and 56 years were genotyped and classified according to absence (TT, n = 15) or presence (CC, n = 15) of the polymorphism. They were randomly selected for the use of placebo or atorvastatin (10 mg/day/14 days). After each treatment lipids, lipoproteins, HDL2 and HDL3 composition, cholesteryl ester transfer protein (CETP) activity, metabolites of NO and hsCRP were evaluated.
  
  
  RESULTS
  The comparisons between genotypes after placebo showed an increase in CETP activity in a polymorphism-dependent way (TT, 12±7; CC, 22±12; p < 0.05). The interaction analyses between treatments indicated that atorvastatin has an effect on cholesterol, LDL, nitrite and lipid-protein ratios (HDL2 and HDL3) (p < 0.001) in both genotypes. Interestingly, we observed genotype/drug interactions on CETP (p < 0.07) and lipoprotein (a) (Lp(a)) (p < 0.056), leading to a borderline decrease in CETP, but with no effect on Lp(a). HsCRP showed no alteration.
  
  
  CONCLUSIONS
  These results suggest that statin treatment may be relevant for primary prevention of atherosclerosis in patients with the T-786C polymorphism of eNOS, considering the effects on lipid metabolism.
authors.affiliation: Departamento de Patologia Clínica, Laboratório de Lípides, Núcleo de Medicina e Cirurgia Experimental, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.
authors.forename: Vanessa Helena de Souza
authors.initials: VH
authors.lastname: Zago
authors.forename: José Eduardo Tanus dos
authors.initials: JE
authors.lastname: Santos
authors.forename: Mirian Regina Gardin
authors.initials: MR
authors.lastname: Danelon
authors.forename: Roger Marcelo Mesquita da
authors.initials: RM
authors.lastname: Silva
authors.forename: Natália Baratella
authors.initials: NB
authors.lastname: Panzoldo
authors.forename: Eliane Soler
authors.initials: ES
authors.lastname: Parra
authors.forename: Fernanda
authors.initials: F
authors.lastname: Alexandre
authors.forename: Vítor Wilson de Moura
authors.initials: VW
authors.lastname: Virgínio
authors.forename: Eder Carlos Rocha
authors.initials: EC
authors.lastname: Quintão
authors.forename: Eliana Cotta de
authors.initials: EC
authors.lastname: Faria
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000032:analysis; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood; D006538:Heptanoic Acids / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000097:blood / Q000187:drug effects / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011758:Pyrroles / Q000097:blood / Q000494:pharmacology*; D016037:Single-Blind Method; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D006538:Heptanoic Acids; D008055:Lipids; D011758:Pyrroles; D009569:Nitric Oxide; D002097:C-Reactive Protein; D000069059:Atorvastatin; D052250:Nitric Oxide Synthase Type III