eNOS T-786C polymorphism affects atorvastatin-induced changes in erythrocyte membrane fluidity.
OBJECTIVE
Statins have pleiotropic effects, including endothelial nitric oxide synthase (eNOS) upregulation and increased nitric oxide formation, which can be modulated by a genetic polymorphism in the promoter region of the eNOS gene (T-786C). Here, we report our investigation of whether this polymorphism modulates the effects of atorvastatin on the fluidity of erythrocyte membranes.


METHODS
We genotyped 200 healthy subjects (males, 18-60 years of age) and then randomly selected 15 of these with the TT genotype and 15 with the CC genotype to receive placebo or atorvastatin (10 mg/day oral administration) for 14 days. Cell membrane fluidity was evaluated by electron paramagnetic resonance (EPR) and spin-labeling method. The EPR spectra were registered on a VARIAN-E4 spectrometer. Thiobarbituric acid-reactive species (TBA-RS) and plasma membrane cholesterol were determined in the erythrocytes.


RESULTS
Atorvastatin reduced membrane fluidity in CC subjects (P < 0.05) but not in those with the TT genotype (P > 0.05). While no significant differences were found in plasma membrane cholesterol concentrations, higher TBA-RS concentrations were found in the CC subjects than in the TT subjects (P < 0.05).


CONCLUSIONS
These findings suggest that a short treatment with atorvastatin is disadvantageous to subjects with the CC genotype for the T-786C polymorphism compared to those with TT genotype, at least in terms of the hemorheological properties of erythrocytes.
Nagassaki
S
S
Departamento de Farmacologia, Faculdade de Medicina de Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
Herculano
R D
RD
Graeff
C F O
CF
Tanus-Santos
J E
JE
D000328:Adult; D000069059:Atorvastatin; D002784:Cholesterol / Q000378:metabolism; D003545:Cysteine; D004578:Electron Spin Resonance Spectroscopy; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D018056:Hemorheology; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects / Q000235:genetics; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D011758:Pyrroles / Q000494:pharmacology*; D013858:Thiobarbiturates / Q000378:metabolism; D013912:Threonine; D055815:Young Adult
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D013858:Thiobarbiturates; D013912:Threonine; D002784:Cholesterol; D000069059:Atorvastatin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D003545:Cysteine; C029684:thiobarbituric acid