POSSIBLE ROLE OF GENETIC POLYMORPHISMS FOR INDIVIDUALSENSITIVITY TO SIMVASTATIN IN INITIAL THERAPEUTIC DOSE


Cite item

Full Text

Abstract

Despite proven benefits of statins their effects and tolerability differ significantly in different patients. Genetic polymorphisms in genes of metabolizing enzymes, especially CYP3A5, and transporter proteins, especially OATP1B1, represent important factor for these changes. In our study we investigated influence of genetic polymorphisms on effects and safety of simvastatin 20 mg daily in 60 patients with dislipidemia. We observed reverse correlation of effects and adverse effects of simvastatin in our patients. Among CYP3A5*1 carriers we observed a tendency to less pronounced lipid-lowering effects (1,2 vs 2,9 mcmol/l). Our data may indicate importance of genetic polymorphisms even when statins are use in minimal therapeutic doses.

About the authors

K A Zagorodnikova

North-Western State Medical University named after I.I. Mechnikov

A A Topanova

North-Western State Medical University named after I.I. Mechnikov

M A Natas

North-Western State Medical University named after I.I. Mechnikov

V A Shumkov

North-Western State Medical University named after I.I. Mechnikov

References

  1. Smith, SC Jr, Benjamin, EJ, Bonow, RO et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation endorsed by the World Heart Federation and the Preventive Cardiovascular Nurses Association // J Am Coll Cardiol. - 2011. - Vol.58. - Iss. 23. - P. 2432-2446.
  2. Smith, S., Judge, H., Peters, G., Armstrong, M., Fontana, P., Gaussem, P., Daly, M., Storey, R. Common sequence variations in the P2Y12 and CYP3A5 genes do not explain the inhibitory effects of clopidogrel therapy // Platelets. - 2006. - V. 17. - P. 250-258.
  3. Тутельян, В.А., Батурин, К.А., Погожева, А.В. Актуальные вопросы диагностики и коррекции нарушений пищевого статуса у больных с сердечно-сосудистой патологией // Consilium Medicum. - 2010. - Т. 12, № 10. URL: http://www.consilium-medicum.com/magazines/magazines/cm/medicum/article/19919 (дата обращения 08.04.2012)
  4. Tachibana-limori, R., Tabata, Y., Kusuhara, H. et al. Effect of genetic polymorphism of OATP-C (SLCO1B1) on lipid-lowering response to HMG-CoA reductase inhibitors // Drug Metab Pharmacokinet. - 2004. - Vol. 19. - Iss.5. - P. 375-380.
  5. Romaine, SPR, Bailey, KM, Hall, AS, Balmforth, AJ The influence of SLCO1B1 (OATP1B1) gene polymorphisms on response to statin therapy // Tha pharmacogenomics journal. - 2010. - №10. - P. 1-11.
  6. Link, E, Parish, J, Armitage, L, et al. SLCO1B1 variants and statin-induced myopathy - a genomewide study // N Engl J Med. - 2008. - Vol.359. - Iss. 8. - P. 789-799.
  7. Neuvonen, PJ, Niemi, M., Backman, JT. Drug interactions with lipid lowering drugs: mechanisms and clinical relevance // Clin Pharmacol Ther. - 2006. - Vol. 80, № 6. - P. 565-581.
  8. Maggo, SDS., Kennedy, MA., Clark, DVJ. Clinical implications of pharmacogenetic variation on the effects of statins // Drug Saf. - 2011. - Vol.34. - № 1. - P. 1-19.
  9. Pearson, TA, Boden, WE. The imperative to raise low levels of high-density lipoprotein in cholesterol--a better clinical strategy in the prevention and treatment of coronary artery disease. Introduction // Am J Cardiol. - 2000. - Vol. 86. - Iss. 12A. - P. 1L - 4L.
  10. Harper, CR, Jacobson, TA. The broad spectrum of statin myopathy: from myalgia to rhabdomyolysis // Curr Opin Lipidol. - 2007. - Vol. 18., - Iss. 4. - P. 401-408.
  11. Law, M, Wald, NJ. Efficacy and safety of cholesterol-lowering treatment // Lancet. - 2006. - Vol. 11. - Iss. 367. - P. 469-470.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2015 Zagorodnikova K.A., Topanova A.A., Natas M.A., Shumkov V.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Согласие на обработку персональных данных

 

Используя сайт https://journals.rcsi.science, я (далее – «Пользователь» или «Субъект персональных данных») даю согласие на обработку персональных данных на этом сайте (текст Согласия) и на обработку персональных данных с помощью сервиса «Яндекс.Метрика» (текст Согласия).