CYP2C19*2, CYP2C19*3, CYP2C19*17 allele and genotype frequencies in clopidogrel-treated patients with coronary heart disease from the Russian population
Abstract
Individual variation in the response to drug therapy has been mainly attributed to the genetic polymorphism of cytochrome P 450 isoenzymes. We examined 40 patients with CHD, who received clopidogrel and 146 healthy volunteers. CYP2C19*2, CYP2C19*3, CYP2C19*17 carriage was determined by a polymerase chain reaction. 20 clopidogrel-treated patients had the CYP2C19 *1/*1 genotype (50%), 12 – CYP2C19 *1/*2 (30,0%), 5 – CYP2C19 *1/*17 (12,5%), and 3 – CYP2C19 *17/*17 (7,5%). Among the healthy volunteers, 111-CYP2C19 *1/*1 (76,1%), 31 – CYP2C19 *1/*2 (21, 2%), and 4 – CYP2C19*2/*2 (2,7%). The frequencies of CYP2C19*2 were 15,0% and 13,3% in patients with CHD and in healthy volunteers respectively (p=0,323). The results of the present study show the impact of individual response variability to clopidogrel on clinical outcomes and may be helpful in developing current and future directions for its management.
About the Authors
K. B. Mirzaev
Первый Московский государственный медицинский университет имени И.М. Сеченова, Москва
Russian Federation
Russian Federation
D. A. Sychev
Первый Московский государственный медицинский университет имени И.М. Сеченова, Москва
Russian Federation
Russian Federation
V. N. Karkischenko
ФГБУН «Научный центр биомедицинских технологий ФМБА России», Московская область
Russian Federation
Russian Federation
A. V. Grachev
«СМ-клиника», Москва
Russian Federation
Russian Federation
G. P. Knyazev
«СМ-клиника», Москва
Russian Federation
Russian Federation
R. E. Kazakov
«СМ-клиника», Москва
Russian Federation
Russian Federation
A. V. Korasev
Первый Московский государственный медицинский университет имени И.М. Сеченова, Москва
Russian Federation
Russian Federation
References
1. Goldstein, J.A. Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. Br. J. Clin. Pharmacol. 2001. 52: 349-355.
2. Mega J.L., Close S.L., Wiviott S.D., Shen L., Hockett R.D., Brandt J.T., et al. Cytochrome p-450 polymorphisms andresponse to clopidogrel. N Engl J Med. 2009 Jan 22;360(4):354-62. Epub. 2008. Dec 22.
3. H.R. Luo, R.E. Poland, K.M. Lin, et al. Genetic polymorphism of cytochrome P450 2C19 in Mexican Americans: a cross-ethnic comparative study. Clin. Pharmacol Ther. 80 (2006). Р. 33-40.
4. Giusti B., Gori A.M., Marcucci R., Saracini C., Sestini I., Paniccia R., et al. Relation of cytochrome P450 2C19 loss-of-function polymorphismto occurrence of drug-eluting coronarystent thrombosis. Am J. Cardiol. 2009 Mar 15;103(6):806-11. Epub 2009. Jan 24.
5. Bonello L., Armero S., Ait Mokhtar O., Mancini J., Aldebert P., Saut N., et al. Clopidogrel loading dose adjustment according to platelet reactivitymonitoring in patients carrying the 2C19*2 loss of function polymorphism. J Am Coll Cardiol. 2010. Nov 9;56(20):1630-6.
6. Sibbing D., Koch W., Gebhard D., et al. Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, andstent thrombosis in clopidogrel-treatedpatients with coronary stent placement. Circulation. 2010. 121:512-518.
7. Trenk D., Hochholzer W., Fromm M.F., et al. Cytochrome P450 2C19 681G >Apolymorphism and high on-clopidogrelplatelet reactivity associated with adverse1-year clinical outcome of elective percutaneous coronary intervention withdrug-eluting or bare-metal stents. J. AmColl Cardiol. 2008. 51:1925-1934.
8. Shuldiner A.R., O’Connell J.R., GurbelP.A., et al. Influence of CYP2C19 polymorphism on antiplatelet effects of clopidogrel and long-term recurrent ischemic event occurrence. JAMA, 302 (2009), Р. 849-858.
9. Simon T., Verstuyft C., Mary-Krause M., Quteineh L., Drouet E., Meneveau N., et al. Genetic determinants of response to 14. Komarov A.L., Panchenko E.P., clopidogrel and cardiovascular events. Donnikov A.E., Shakhmatova O.O., N Engl J Med 2009. 360(4):363-375.Dzhalilova G.V., Iliushchenko T.A.
10. Sibbing D., Stegherr J., Latz W., et Factors determining clinical effectivenessal. Cytochrome P450 2C19 loss-of-of clopidogrel and prognosis of patientsfunction polymorphism and stent with stable ischemic heart disease. thrombosis following percutaneous Kardiologiia. 2011. 51(2):8-18. coronary intervention Eur Heart J, 30 15. Gaikovitch E.A., Cascorbi I., Mrozi( 2009), Р. 916-922. kiewicz P.M., Brockmoller J., Frotschl
11. ESC Guidelines for the management of R., Kopke K., et al. Polymorphisms of acute coronary syndromes in patients drug-metabolizing enzymes CYP2C9, presenting without persistent ST-CYP2C19, CYP2D6, CYP1A1, NAT2 segment elevation: The Task Force and of P-glycoprotein in a Russian for the management of acute coronary population. Eur J. Clin. Pharmacol. syndromes (ACS) in patients presenting 2003. Aug;59(4):303-12. Epub 2003. without persistent ST-segment elevation Jul 15. of the European Society of Cardiology 16. Galiavich A.S., Valeeva D.D., (ESC). Eur Heart J. 2011. Sep 21. Minnetdinov R.Sh., Arkhipova A.A.,
12. ACCF/AHA/SCAI Guideline for Akhmetov I.I., Galiavi RA. CYP2C19 Percutaneous Coronary Intervention. gene polymorphism in patients with JACC. 2011. V.58(24). P.44-122.myocardial infarction who use clopidogrel.
13. Angiolillo D.J., Fernandez-Ortiz Kardiologiia. 2012. 52(4):20-4. A., Bernardo E., et al. Variability in17. Collet J.P., Hulot J.S., Pena A., et al. individual responsiveness to clopidogrel:Cytochrome P450 2C19 polymorphismclinical implications, management, andin young patients treated with clopidogrelfuture perspectives. J Am Coll Cardiol.after myocardial infarction: a cohort 2007. 49(14):1505-1516. study. Lancet. 2009. 373:309-317.
14. Komarov A.L., Panchenko E.P., Donnikov A.E., Shakhmatova O.O., Dzhalilova G.V., Iliushchenko T.A. Factors determining clinical effectiveness of clopidogrel and prognosis of patients with stable ischemic heart disease. Kardiologiia. 2011. 51(2):8-18.
15. Gaikovitch E.A., Cascorbi I., Mrozikiewicz P.M., Brockmöller J., Frötschl R., Köpke K., et al. Polymorphisms of drug-metabolizing enzymes CYP2C9, CYP2C19, CYP2D6, CYP1A1, NAT2 and of P-glycoprotein in a Russian population. Eur J. Clin. Pharmacol. 2003. Aug;59(4):303-12. Epub 2003. Jul 15.
16. Galiavich A.S., Valeeva D.D., Minnetdinov R.Sh., Arkhipova A.A., Akhmetov I.I., Galiavi RA. CYP2C19 gene polymorphism in patients with myocardial infarction who use clopidogrel. Kardiologiia. 2012. 52(4):20-4.
17. Collet J.P., Hulot J.S., Pena A., et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet. 2009. 373:309-317.
Review
For citations:
Mirzaev K.B., Sychev D.A., Karkischenko V.N., Grachev A.V., Knyazev G.P., Kazakov R.E., Korasev A.V. CYP2C19*2, CYP2C19*3, CYP2C19*17 allele and genotype frequencies in clopidogrel-treated patients with coronary heart disease from the Russian population. Journal Biomed. 2013;1(1):117-122. (In Russ.)
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