Genetics
Baseline CETP activity nearly doubles in carriers of the eNOS T-786C polymorphism, atorvastatin crossover study finds (Arq Bras Cardiol 2013)
Original title: Effects of atorvastatin and T-786C polymorphism of eNOS gene on plasma metabolic lipid parameters
This randomized study evaluated whether the eNOS T-786C polymorphism modifies the effects of atorvastatin on lipid profile, nitric oxide metabolites, and high-sensitivity C-reactive protein, in thirty asymptomatic male volunteers genotyped as TT (n=15) or CC (n=15) and randomly assigned to placebo or atorvastatin (10 mg/day for 14 days) in each treatment phase, with CETP activity measured alongside other parameters. After placebo, CETP activity was higher in CC carriers than TT carriers in a polymorphism-dependent way (TT 12 plus or minus 7; CC 22 plus or minus 12; p less than 0.05). Atorvastatin affected cholesterol, LDL, nitrite, and HDL2/HDL3 ratios in both genotypes (p less than 0.001), and a genotype-by-drug interaction trend was observed for CETP (p less than 0.07), leading to a borderline decrease in CETP activity, though this did not reach statistical significance. High-sensitivity C-reactive protein showed no change with treatment.
Original 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.
Conclusion: 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.