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. 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.