Analysis of genetic aspects of therapy with Rosuvastatin

Анализ генетических аспектов при терапии розувастатином
Samat Kozhakhmetov 1, Almagul Kushugulova 1, Akbota Kakimova 1, Talgat Nurgozhin 1, Zhaksybay Zhumadilov 1
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1 Nazarbayev University, National Laboratory Astana, Laboratory of Experimental and Clinical Pharmacology, Astana, Kazakhstan
J CLIN MED KAZ, Volume 2, Issue 40, pp. 22-26.
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Statins widely used in clinical practice in decreasing the level of lipids in blood plasma. Difference of response for therapy may be associated with structural changes in genes of metabolism of drugs. Main polymorphisms of genes of metabolism which impact on effectiveness and security of rosuvastatin are studied in review.


Kozhakhmetov S, Kushugulova A, Kakimova A, Nurgozhin T, Zhumadilov Z. Analysis of genetic aspects of therapy with Rosuvastatin. Journal of Clinical Medicine of Kazakhstan. 2016;2(40):22-6.


  • Meshkov A.N. Gipolipidemicheskaya effektivnost’ rosuvastatina v sravnenii s drugimi statinami (Lipid-lowering efficacy of rosuvastatin compared with other statins), Ratsyonal’naya farmakoterapiya v kardiologii, 2012, Vol. 8, No 5, pp. 691-693.
  • Wolffenbuttel B.H., Franken A.A., Vincent H.H. Cholesterol-lowering effects of rosuvastatin compared with atorvastatin in patients with type 2 diabetes - CORALL study, J Intern Med.,2005, Vol. 257, No.6, pp. 531-539.
  • Betteridge D.J., Gibson J.M., Sager P.T. Comparison of effectiveness of rosuvastatin versus atorvastatin on the achievement of combined C-reactive protein (<2 mg/L) and low-density lipoprotein cholesterol (< 70 mg/dl) targets in patients with type 2 diabetes mellitus (from the ANDROMEDA study), Am J Cardiol., 2007,Vol. 100, No. 8, pp. 1245-1248.
  • Berne C., Siewert-Delle A. Comparison of rosuvastatin and atorvastatin for lipid lowering in patients with type 2 diabetes mellitus: results from the URANUS study, Cardiovasc Diabetol., 2005, Vol. 4, p.7.
  • Wijndaele K., Duvigneaud N., Matton al. Sedentary behaviour, physical activity and a continuous metabolic syndrome risk score in adults, Eur J Clin Nutr., 2009. Vol. 63, No 3, pp. 421-429.
  • Cameron A.J., Shaw J.E., Zimmet P.Z. The metabolic syndrome: prevalence in worldwide populations, Endocrinology and Metabolism Clinics of North America, 2004, Vol. 33, No 2, pp. 351-375. 
  • Vattikuti S., Guo J., Chow C.C. Heritability and genetic correlations explained by common SNPs for metabolic syndrome traits, PLoS Genet., 2012, Vol. 8, No 3, pp. e1002637.
  • Ford E.S., Li C., Zhao G. Prevalence and correlates of metabolic syndrome based on a harmonious definition among adults in the US, J Diabetes, 2010, Vol. 2, No 3. pp. 180-193.
  • Vernay M., Salanave B., de Peretti al. Metabolic syndrome and socioeconomic status in France: The French Nutrition and Health Survey (ENNS, 2006-2007), Int J Public Health, 2013, Vol. 58, No 6. pp. 855-864.
  • Salas R., Bibiloni Mdel M., Ramos al. Metabolic syndrome prevalence among Northern Mexican adult population, PLoS One, 2014, Vol. 9, No 8. pp. e105581.
  • El Brini O., Akhouayri O., Gamal al. Prevalence of metabolic syndrome and its components based on a harmonious definition among adults in Morocco,Diabetes Metab Syndr Obes., 2014, Vol. 7. pp. 341-346.
  • Xi B., He D., Hu al. Prevalence of metabolic syndrome and its influencing factors among the Chinese adults: the China Health and Nutrition Survey in 2009, Prev Med., 2013, Vol. 57, No 6. pp. 867-871.
  • Aljohani N. Metabolic syndrome: Risk factors among adults in Kingdom of Saudi Arabia, J Family Community Med., 2014, Vol. 21, No 3, pp. 170-175.
  • Gundogan K., Bayram F., Capak al. Prevalence of metabolic syndrome in the Mediterranean region of Turkey: evaluation of hypertension, diabetes mellitus, obesity, and dyslipidemia, Metab Syndr Relat Disord., 2009, Vol. 7, Vol. 9, No 5. pp. 427- 434.
  • Azizi F., Salehi P., Etemadi al. Prevalence of metabolic syndrome in an urban population: Tehran Lipid and Glucose Study, Diabetes Res Clin Pract., 2003, Vol. 61, Vol. 9, No 1. pp. 29-37.
  • Desroches S., Lamarche B. The evolving definitions and increasing prevalence of the metabolic syndrome, Applied Physiology, Nutrition, and Metabolism, 2007, Vol. 32, No 1. pp. 23-32.
  • Kolovou G.D., Anagnostopoulou K.K., Salpea al. The Prevalence of Metabolic Syndrome in Various Populations, The American Journal of the Medical Sciences, 2007, Vol. 333, No 6. pp. 362-371.
  • Abylayuly Zh., Dzhusipov A.K., Berkinbayev C.F. Proekt konsensusa po diagnostike i vedeniu metabolicheskogo sindroma v RK. Razrabotan po rezul’tatam rezolutsii Respublikanskoy nauchno-prakticheskoy konferentsii ‘’Metabolicheskiy sindrom. Realii i perspektivy v kardiologii i endokrinologii’’ (Draft consensus on the diagnosis and management of metabolic syndrome in the Republic of Kazakhstan. A resolution on the results of the Republican scientific-practical conference «The metabolic syndrome. Realities and Perspectives in Cardiology and Endocrinology»), Terapevticheskiy vestnik, 2008, Vol. 4, No 20. pp. 27-32.
  • Zimmet P., Alberti K.G.M.M., Kaufman al. The metabolic syndrome in children and adolescents – an IDF consensus report, Pediatric Diabetes. 2007, Vol. 8, pp. 299-306.
  • Park Y., Zhu S., Palaniappan al. The metabolic syndrome: Prevalence and associated risk factor findings in the us population from the third national health and nutrition examination survey, 1988-1994, Archives of Internal Medicine, 2003, Vol. 163, No 4. pp. 427-436.
  • Hu G., Qiao Q., Tuomilehto al. Plasma insulin and cardiovascular mortality in non-diabetic European men and women: a meta-analysis of data from eleven prospective studies, Diabetologia, 2004, Vol. 47, No 7. pp. 1245-1256.
  • Carr D.B., Utzschneider K.M., Hull al. Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome, Diabetes, 2004, Vol. 53, Vol. 9, No 8. pp. 2087-2094.
  • Saad M.F., Lillioja S., Nyomba al. Racial differences in the relation between blood pressure and insulin resistance, N Engl J Med., 1991, Vol. 324, No 11. pp. 733-739.
  • Anderson P.J., Critchley J.A., Chan al. Factor analysis of the metabolic syndrome: obesity vs insulin resistance as the central abnormality, Int J Obes Relat Metab Disord., 2001, Vol. 25, No 12. pp. 1782-1788.
  • Laakso M. Gene variants, insulin resistance, and dyslipidaemia, Current Opinion in Lipidology, 2004, Vol. 15, No 2, pp. 115- 120.
  • Poulsen P., Levin K., Petersen al. Heritability of insulin secretion, peripheral and hepatic insulin action, and intracellular glucose partitioning in young and old Danish twins, Diabetes, 2005, Vol. 54, No 1. pp. 275-283.
  • Koh K.K. Effects of statins on vascular wall: vasomotor function, inflammation, and plaque stability, Cardiovasc Res., 2000, Vol. 47, No 4. pp. 648-657.
  • Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report, Circulation, 2002, Vol. 106, No 25. pp. 3143-3421.
  • Jones P.H., Davidson M.H., Stein al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial), Am J Cardiol., 2003, Vol. 92, No 2. pp. 152-160.
  • Kim R.B. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) and genetic variability (single nucleotide polymorphisms) in a hepatic drug uptake transporter: what’s it all about? Clin Pharmacol Ther., 2004, Vol. 75, No 5. pp. 381- 385.
  • Kitamura S., Maeda K., Wang al. Involvement of multiple transporters in the hepatobiliary transport of rosuvastatin, Drug Metab Dispos., 2008, Vol. 36, No 10. pp. 2014-2023.
  • Ho R.H., Kim R.B. Transporters and drug therapy: implications for drug disposition and disease, Clin Pharmacol Ther., 2005, Vol. 78, No 3. pp. 260-277.
  • Pasanen M.K., Neuvonen P.J., Niemi M. Global analysis of genetic variation in SLCO1B1, Pharmacogenomics, 2008, Vol. 9, No 1. pp. 19-33.
  • Awan Z., Seidah N.G., MacFadyen al. Rosuvastatin, proprotein convertase subtilisin/kexin type 9 concentrations, and LDL cholesterol response: the JUPITER trial, Clin Chem., 2012, Vol. 58, No 1. pp. 183-189. 
  • Ference B.A., Yoo W., Alesh al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis, J Am Coll Cardiol., 2012, Vol. 60, No 25. pp. 2631-2639.
  • Barber M.J., Mangravite L.M., Hyde al. Genome-wide association of lipid-lowering response to statins in combined study populations, PLoS One, 2010, Vol. 5, No 3. pp. e9763.
  • Mangravite L.M., Thorn C.F., Krauss R.M. Clinical implications of pharmacogenomics of statin treatment, Pharmacogenomics J., 2006, Vol. 6, No 6. pp. 360-374.
  • Tomlinson B., Hu M., Lee al. ABCG2 polymorphism is associated with the low-density lipoprotein cholesterol response to rosuvastatin, Clin Pharmacol Ther., 2010, Vol. 87, No 5. pp. 558-562.
  • Hu M., Lui S.S., Mak al. Pharmacogenetic analysis of lipid responses to rosuvastatin in Chinese patients, Pharmacogenet Genomics, 2010, Vol. 20, No 10. pp. 634-637.
  • Hubacek J.A., Adamkova V., Prusikova al. Impact of apolipoprotein A5 variants on statin treatment efficacy, Pharmacogenomics, 2009, Vol. 10, No 6. pp. 945-950.
  • Lee E., Ryan S., Birmingham al. Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment, Clin Pharmacol Ther., 2005, Vol. 78, No 4. pp. 330-341.