eNOS T-786C polymorphism affects atorvastatin-induced changes in erythrocyte membrane fluidity
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Data
2009-04-01
Autores
Nagassaki, S.
Herculano, R. D.
Graeff, Carlos Frederico de Oliveira [UNESP]
Tanus-Santos, J. E.
Título da Revista
ISSN da Revista
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Editor
Springer
Resumo
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.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.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).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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Palavras-chave
Endothelial nitric oxide synthase, EPR, Genotypes, Nitric oxide, Polymorphisms, Statins
Como citar
European Journal of Clinical Pharmacology. New York: Springer, v. 65, n. 4, p. 385-392, 2009.