eNOS T-786C polymorphism affects atorvastatin-induced changes in erythrocyte membrane fluidity |
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Authors: | S Nagassaki R D Herculano C F O Graeff J E Tanus-Santos |
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Institution: | (1) Departamento de Farmacologia, Faculdade de Medicina de Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirao Preto, SP, Brazil;(2) Departamento de Física e Matemática, Faculdade de Filosofia, Ciencias e Letras de Ribeirao Preto, University of Sao Paulo, 14040-901 Ribeirao Preto, SP, Brazil;(3) Departamento de Física, Faculdade de Ciências de Bauru, University of Estadual Paulista, 17033-360 Bauru, SP, Brazil |
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Abstract: | Purpose 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. |
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Keywords: | Endothelial nitric oxide synthase EPR Genotypes Nitric oxide Polymorphisms Statins |
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