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Gene polymorphism of SLCO1B1, associated with the developmentof statin-induced myopathy, leves of vitamin d in russian patients with hyperlipidemia

Authors: G.N. Shuev 1, D.A. Sychev 2, A.V. Grachev 3

Company: 1 I.M. Sechenov First Moscow State Medical University Ministry of Health of the Russian Federation; ul. Trubetskaya, 8, str. 2, Moscow, 119991, Russian Federation;
2 Russian Medical Academy of Postgraduate Education; ul. Barrikadnaya, 2/1, Moscow, 125993, Russian Federation;
3 Multidisciplinary Medical Holding «CM-Clinic»; ul. Priorova, 36, Moscow, 125130, Russian Federation.


DOI: https://doi.org/10.15275/kreatkard.2015.04.05

For citation: Shuev GN, Sychev DA, Grachev AV. Gene polymorphism of SLCO1B1, associated with the development of statin-induced myopathy, leves of vitamin d in russian patients with hyperlipidemia. Kreativnaya Kardiologiya. 2015; 4: 40-45 (in Russian)

Keywords: pharmacogenetics SLCO1B1 statins myopathy vitamin D

Full text:  

 

Abstract

Statins are the most commonly prescribed medicines for treatment of hypercholesterolemia. At the same time up to 25% patients cannot tolerate or discontinue statin therapy due to statin-induced side effects. In majority of cases side-effects are attributed to SLCO1B1 gene mutation. Our research was focused on the frequency of the SLCO1B1*5 genetic variant in the Russian population.

Material and methods. 1071 patients with hyperlipidemia were included into the study. Genotypes of SLCO1B1*5 (с.521Т>С, rs4149056) were determined with polymerase chain reaction (PCR) amplification. Our data was compared to admissible data from Brazil and China. We determined the level of 25(OH)D in the blood plasma by high performance liquid chromatography in 39 patients receiving statins for 3 months or more.

Results. 665 (62%) patients had ТТ genotype of allelic variant SLCO1B1*5, 346 (32%) participants had ТС, СС variant was found in 60 patients (6%). As compared with data from Brazil and China, allele C frequency which causes an increased risk of statin-induced myopathy was found significantly more often in the Russian population. The «carrier» and «not carrier» C allele statistically significant differences in the levels of 25(OH)D was not found: 32.3±13.4 vs 40.3±10.8 nmol/l, p=0.299.

Conclusion. Pharmacogenetic testing (genotyping SLCO1B1*5) can be used in Russian patients with hyperlipidemia for calculations of maximal tolerated dose in accordance with the recommendations of ESF experts. More data are needed to assess the relationship between carriage of C allele and the level of 25(OH)D.

References

  1. Baigent C., Keech A., Kearney P.M., Blackwell L., Buck G., Pollicino C. et al. Efficacy and safety of cholesterol-lowering treatment: prospective metaanalysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005; 366 (9493): 1267–78.

  2. Bays H. Statin safety: an overview and assessment of the data-2005. Am. J. Cardiol. 2006; 97 (8A): 6C–26C.

  3. Canestaro W.J., Austin M.A., Thummel K.E. Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review. Genet Med. 2014.

  4. Nishizato Y., Ieiri I., Suzuki H., Kimura M., Kawabata K., Hirota T. et al. Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics. Clinical Pharmacology & Therapeutics. 2003; 73 (6): 554–65.

  5. Tirona R.G., Leake B.F., Merino G., Kim R.B. Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. J. Biol. Chem. 2001; 276 (38): 35669–75.

  6. Carr D.F., O'Meara H., Jorgensen A.L., Campbell J., Hobbs M., McCann G. et al. SLCO1B1 Genetic Variant Associated With Statin-Induced Myopathy: A Proof-of-Concept Study Using the Clinical Practice Research Datalink. Clinical Pharmacology & Therapeutics. 2013; 94 (6): 695–701.

  7. Linde R., Peng L., Desai M., Feldman D. The role of vitamin D and SLCO1B1*5 gene polymorphism in statin-associated myalgias. Dermatoendocrinology. 2010; 2 (2): 77–84.

  8. Voora D., Shah S.H., Spasojevic I., Ali S., Reed C.R., Salisbury B.A. et al. The SLCO1B1*5 genetic variant is associated with statin-induced side effects. J. Am. Coll. Cardiol. 2009; 54 (17): 1609–16.

  9. SEARCH Collaborative Group, Link E., Parish S., Armitage J., Bowman L., Heath S. et al. SLCO1B1 variants and statin-induced myopathy a genomewide study. New Engl. J. Med. 2008; 359 (8): 789–99.

  10. De Keyser C.E., Peters B.J., Becker M.L., Visser L.E., Uitterlinden A.G., Klungel O.H. et al. The SLCO1B1 c.521T>C polymorphism is associated with dose decrease or switching during statin therapy in the Rotterdam Study. Pharmacogenet Genomics. 2014; 24 (1): 43–51.

  11. Becquemont L., Alfirevic A., Amstutz U., Brauch H., Jacqz-Aigrain E., Laurent-Puig P. et al. Practical recommendations for pharmacogenomics-based prescription: 2010 ESF-UB Conference on Pharmacogenetics and Pharmacogenomics. Pharmacogenomics. 2011; 12 (1): 113–24.

  12. Сироткина А.М., Хохлов А.Л., Воронина Е.А., Могутов М.С., Дряженкова И.В., Царева И.Н. и др. Распространенность полиморфного маркера гена SLCO1B1 у пациентов с дислипидемией и системным атеросклерозом. Кардиоваскулярная терапия и профилактика. 2013; 22

  13. Pasanen M.K1, Neuvonen P.J., Niemi M. Global analysis of genetic variation in SLCO1B1. Pharmacogenomics. 2008; 9 (1): 19–33.

  14. Sortica V.A., Fiegenbaum M., Lima L.O., Van der Sand C.R., Van der Sand L.C., Ferreira M.E. et al. SLCO1B1 gene variability influences lipid-lowering efficacy on simvastatin therapy in Southern Brazilians. Clin. Chem. Lab. Med. 2012; 50 (3): 441–8.

  15. Lee H.K., Hu M., Lui S.Sh., Ho C.S., Wong C.K., Tomlinson B. Effects of polymorphisms in ABCG2, SLCO1B1, SLC10A1 and CYP2C9/19 on plasma concentrations of rosuvastatin and lipid response in Chinese patients. Pharmacogenomics. 2013; 14 (11): 1283–94.

  16. Lee H.K., Hu M., Lui S.Sh., Ho C.S., Wong C.K., Tomlinson B. Lack of association between SLCO1B1 polymorphism and the lipid-lowering effects of atorvastatin and simvastatin in Chinese individuals. Eur. J. Clin. Pharmacol. 2013; 69 (6): 1269–74.

  17. Yang G.P., Yuan H., Tang B., Zhang W., Wang L.S., Huang Z.J. et al. Lack of effect of genetic polymorphisms of SLCO1B1 on the lipid-lowering response to pitavastatin in Chinese patients. Acta Pharmacol. Sin. 2010; 31 (3): 382–6.

  18. Ullman-Cullere M.H., Mathew J.P. Emerging landscape of genomics in the Electronic Health Record for personalized medicine. Human Mutation. Variation, Informatics and Disease. 2011; 32 (5): 512–6.

  19. Swen J.J., Nijenhuis M., de Boer A., Grandia L., Maitland-van der Zee A.H., Mulder H. et al. Pharmacogenetics: from bench to byte–an update of guidelines. Clin. Pharmacol. Ther. 2011; 89 (5): 662–73.

  20. Relling M.V., Klein T.E. CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. Clin. Pharmacol. Ther. 2011; 89 (3): 464–7.

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery


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