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eNOS T-786C polymorphism affects atorvastatin-induced changes in erythrocyte membrane fluidity

  • Pharmacogenetics
  • Published:
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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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Acknowledgments

The authors wish to thank Dr. Pietro Ciancaglini and Ana Maria Sper Simão, Chemical Department, FFCLRP, Sao Paulo University, Ribeirao Preto, SP – Brazil, for their technical assistance with the experimental procedures. This study was funded by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP-Brazil) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-Brazil).

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Authors and Affiliations

  1. Departamento de Farmacologia, Faculdade de Medicina de Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil

    S. Nagassaki & J. E. Tanus-Santos

  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

    R. D. Herculano

  3. Departamento de Física, Faculdade de Ciências de Bauru, University of Estadual Paulista, 17033-360, Bauru, SP, Brazil

    C. F. O. Graeff

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  1. S. Nagassaki
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  2. R. D. Herculano
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  3. C. F. O. Graeff
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  4. J. E. Tanus-Santos
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Correspondence to J. E. Tanus-Santos.

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Nagassaki, S., Herculano, R.D., Graeff, C.F.O. et al. eNOS T-786C polymorphism affects atorvastatin-induced changes in erythrocyte membrane fluidity. Eur J Clin Pharmacol 65, 385–392 (2009). https://doi.org/10.1007/s00228-008-0602-7

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  • DOI: https://doi.org/10.1007/s00228-008-0602-7

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