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The frequency of CYP2C19 allelic variants in patientswith acute coronary syndrome in central, eastern,northern Siberia and Moscow region

Authors: Mirzaev K.B.1, Zelenskaya E.М.2, Barbarash O.L.3, Ganyukov V.I.3, Kochergin N.A.3, Apartsin K.A.4, 5, Saraeva N.O.4, Gorohova A.V.4, 5, Nikolaev K.Yu.6, 7, Batueva K.Yu.8, Konova O.D.1, Grishina E.A.1, Ryzhikova K.A.1, Sozaeva Zh.A.1, Gilyarov M.Yu.9, Andreev D.A.9, Lifshits G.I. 2, 5, 7, Sychev D.A.1

Company: 1 Russian Medical Academy of Postgraduate Education of Ministry of Health of the Russian Federation; ulitsa Barrikadnaya, 2/1, Moscow, 123995, Russian Federation;
2 Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences; prospekt Akademika Lavrent'eva, 8, Novosibirsk, 630090, Russian Federation;
3 Research Institute for Complex Issues of Cardiovascular Diseases, Siberian Branch of the Russian Academy of Sciences; Sosnovyy bul'var, 6, Kemerovo, 650002, Russian Federation;
4 Irkutsk Regional Badge of Honour Clinical Hospital; mikrorayon Yubileynyy, 100, Irkutsk, 664049, Russian Federation;
5 Irkutsk Research Center, Siberian Branch of the Russian Academy of Sciences; ulitsa Lermontova, 134, Irkutsk, 664033, Russian Federation;
6 Research Institute of Internal and Preventive Medicine; ulitsa Bogatkova, 175/1, Novosibirsk, 630089, Russian Federation;
7 Novosibirsk National Research State University; ulitsa Pirogova, 2, Novosibirsk, 630090, Russian Federation;
8 Surgut State University of Ministry of Education of the Russian Federation; prospekt Lenina, 1, Surgut, 628412, Russian Federation;
9 Sechenov I.M. First Moscow State Medical University of Ministry of Health of the Russian Federation; ulitsa Trubetskaya, 8/2, Moscow, 119991, Russian Federation

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DOI: https://doi.org/10.15275/kreatkard.2017.01.02

For citation: Mirzaev K.B., Zelenskaya E.М., Barbarash O.L., Ganyukov V.I., Kochergin N.A., Apartsin K.A., Saraeva N.O., Gorokhova A.V., Nikolaev K.Yu., Batueva K.Yu., Konova O.D., Grishina E.A., Ryzhikova K.A., Sozaeva Zh.A., Gilyarov M.Yu., Andreev D.A., Lifshits G.I., Sychev D.A. The frequency of CYP2C19 allelic variants in patients with acute coronary syndrome in Central, Eastern, Northern Siberia and Moscow region. Kreativnaya kardiologiya (Creative Cardiology, Russian journal). 2017; 11 (1): 8–19 (in Russ.). DOI: 10.15275/kreatkard.2017.01.02

Keywords: сlopidogrel аcute coronary syndrome CYP2C19 gene resistance to сlopidogrel ethnic differences

Full text:  

 

Abstract

Objective. An important aspect of current cardiology practice is resistance to clopidogrel – P2Y12-receptor blocker prescribed in a part of dual antiplatelet therapy for prevention of thrombosis of the stent in patients after ACS. The purpose of this review is to study in Moscow and the Siberian regions of frequencies “slow” allele CYP2C19 gene associated with resistance to clopidogrel, and “rapid” allele associated with the risk of bleeding.
Material and methods. The study included 512 residents of large cities in Central (Novosibirsk, Kemerovo), the East (Irkutsk), North (Surgut), Siberia and Moscow region with acute coronary syndrome undergoing percutaneous coronary intervention. The average age of the patients was 63.9±10.9 years. The proportion of men was 80% (409 people), women – 20% (103 people). All patients received dual antiplatelet therapy has been designated as part of a comprehensive drug therapy. Patients received clopidogrel 300 mg – loading, 75 mg – supports. All patients pharmacogenetic testing was conducted using the polymerase chain reaction in real time to determine the alleles CYP2C19*2, CYP2C19*3 and CYP2C19*17.
Results. Among the patients, residents of North, Central, Eastern Siberia and Moscow region carrier frequency of allelic variants of CYP2C19*2 – CYP2C19*3 – CYP2C19*17 was 14.9 – 0.5 – 33.3%, 11.05 – 0.0 – 17.1%, 10.6 – 2.85 – 22.2%, 8 – 0.0 – 15.4%, respectively. In assessing the significance of differences in frequency carrier “slow” and “papid” allelic variants of CYP2C19 gene between patients Russian ethnic group from 4 different regions using the Fisher's exact test, significant differences were obtained only between patients from Central and Eastern by Siberia CYP2C19*3 (p=0.001, odds ratio (OR): 1.05 (95% confidence interval (CI): 1.01–1.09). Сonclusion. The frequency of the minor allele of CYP2C19*2 ranged from 8.0 to 14.9% in different Russian regions, but the differences were not significant. The frequency of allele CYP2C19*3 ranged from 0.5 to 2.8%, while the frequency of this allele in East and Central Siberia differed significantly, it is likely due to the large number of Buryats living in Eastern Siberia. The frequency of allele CYP2C19*17 ranged from 15.4 to 33.3%.

References

  1. Top 10 causes of death in the world. News bulletin.Available at: http://www.who.int/mediacentre/factsheets/fs310/ru/ (accessed 21 November 2016)(in Russ.).
  2. Mancia G., Fagard R., Narkiewicz K. и др. Рекомендации по лечению артериальной гиперто-нии ESH/ESC 2013. Российский кардиологический журнал.2014; 1: 7–94.
  3. Mega J.L., Simon T., Collet J.P. et al. Reduced-function CYP2C19 genotype and risk of adverseclinical outcomes among patients treated withclopidogrel predominantly for PCI: a meta-analy-sis. JAMA. 2010; 304 (1): 1821–30.
  4. Ahmad T., Voora, D., Becker, R.C. The pharmaco-genetics of antiplatelet agents: towards personal-ized therapy? Nat. Rev. Cardiol.2011; 8 (10):560–71.
  5. Harmsze A.M., van Werkum J.W., ten Berg J.M.et al. CYP2C19*2 and CYP2C9*3 alleles are asso-ciated with stent thrombosis: a case–control study.Eur. Heart J.2010; 31 (24): 3046.
  6. Sibbing D., Stegherr J., Latz W. et al. Cytochro-me P450 2C19 loss-of-function polymorphismand stent thrombosis following percutaneous co-ronary intervention. Eur. Heart J.2009; 30 (8):916–22.
  7. Scott S.A., Sangkuhl K., Stein C.M. et al. ClinicalPharmacogenetics Implementation Consortiumguidelines for CYP2C19 genotype and clopidogreltherapy: 2013 Update.Сlin. Pharmacol. Therap.2013; 94 (3): 317–23.
  8. Lifshits G.I., Danilkina S.T., Gus'kova E.V. et al.The association of genes encoding proteins ofhemostasis, with the parameters of hemostasis andperipheral predisposition to atherothromboticevents in patients with cardiovascular disease.Kardiovaskulyarnaya terapiya i profilaktika.2011;4: 90–6 (in Russ.).
  9. Mirzaev K.B., Sychev D.A., Karkischenko V.N.et al. CYP2C19*2, CYP2C19*3, CYP2C19*17allele and genotype frequencies in clopidogrel-treated patients with coronary heart disease fromthe russian population. Biomeditsina. 2013; 2:117–28 (in Russ.).
  10. Komarov A.L., Shakhmatova O.O., Ilyushchen-ko T.A. et al. Assessment of the risk of cardiovascu-lar complications in patients with stable coronaryartery disease receiving clopidogrel: Platelet func-tion or genetic research? Doktor.Ru.2012; 6: 11–9(in Russ.).
  11. Muslimova E.F. Molecular-genetic factors of com-plications after coronary artery stenting in patientswith chronic ischemic heart disease: Med. Sci.Diss. Tomsk; 2016 (in Russ.).
  12. Khalikova A.R., Arkhipova A.A., Akhmetov I.I.et al. The study of cytochrome P-450 CYP2C19gene polymorphisms in population of Tatars livingin Republic of Tatarstan. Prakticheskaya Meditsina.2012; 3 (58): 53–5 (in Russ.).
  13. Kantemirova B.I., Timofeeva N.V., Sychev D.A.et al. A comparative study of CYP2C19 gene poly-morphism in children living in the Astrakhanianregion. Astrakhanskiy meditsinskiy zhurnal.2011; 3:153–5 (in Russ.).
  14. Makeeva O., Stepanov V., Puzyrev V. et al. Globalpharmacogenetics: genetic substructure of Eura-sian populations and its effect on variants of drug-metabolizing enzymes. Pharmacogenomics. 2008;9 (7): 847–68.
  15. Romodanovsky D.P., Khapaev B.A., Ignatiev I.V.et al. Frequencies the “slow” allele variants of thegenes coding isoenzymes of cytochrome Р450CYP2D6, CYP2C19, CYP2C9 in Karachaevs andCircassians. Biomeditsina. 2010; 2: 33–7 (in Russ.).
  16. Mirzaev K.B. Genotyping and phenotyping isoen-zyme of cytochrome P-450 to predict the antiplateletaction of clopidogrel in acute coronary syndrome:clinical and ethnic aspects: Med. Sci. Diss. Moscow;2016 (in Russ.).
  17. Barysheva V.O., Ketova G.G. Pharmacogenetictesting in population of South Ural. Int. J. Risk Saf.Med. 2015; 27 (Suppl. 1): S25–6. DOI: 10.3233/JRS-150677.
  18. Kaneko A., Lum J.K., Yaviong J. et al. High andvariable frequencies of CYP2C19 mutations: med-ical consequences of poor drug metabolism inVanuatu and other Pacific islands. Pharmacogene-tics. 1999; 5: 581–90.
  19. Kupstyte N., Zaliunas R., Tatarunas V. et al. Effectof clinical factors and gene polymorphisms of CYP2C19*2, *17 and CYP4F2*3 on early stentthrombosis. Pharmacogenomics. 2015; 16 (3):181–9.
  20. Denisenko N.P., Sychev D.A., Sizova Zh.M. et al.High frequency of CYP2C19 ultrarapid metaboliz-ers in russian patients with peptic ulcer. Experim.Clin. Gastroenterol. 2015; 6: 11–5.
  21. Federal Service of State Statistics. The results ofNational Population Census 2010. Available at:http://www.gks.ru/free_doc/new_site/perepis2010/croc/Documents/Vol4/pub-04-01.pdf (accessed29 November 2016) (in Russ.)

About Authors

  • Mirzaev Karin Badavievich, MD, PhD, Senior Research Associate, Clinical Pharmacologist;
  • Zelenskaya Elena Mikhaylovna, Research Associate;
  • Barbarash Ol’ga Leonidovna, MD, DM, Professor, Corresponding Member of Russian Academy of Sciences, Director;
  • Ganyukov Vladimir Ivanovich, MD, DM, Professor, Chief of Laboratory;
  • Kochergin Nikita Aleksandrovich, Research Associate;
  • Apartsin Konstantin Anatol’evich, MD, DM, Professor, Chief of Department, Chief of Laboratory;
  • Saraeva Natal’ya Orestovna, MD, DM, Deputy Chief Physician;
  • Gorokhova Anna Vladislavovna, Junior Research Associate;
  • Nikolaev Konstantin Yur’evich, MD, DM, Professor, Chief of Laboratory;
  • Batueva Kristina Yur’evna, Junior Research Associate;
  • Konova Ol’ga Dmitrievna, Resident Physician;
  • Grishina Elena Anatol’evna, MD, PhD, Leading Research Associate;
  • Ryzhikova Kristina Anatol’evna, Junior Research Associate;
  • Sozaeva Zhannet Alimovna, Student;
  • Gilyarov Mikhail Yur’evich, MD, DM, Professor, Deputy Chief Physician;
  • Andreev Denis Anatol’evich, MD, DM, Professor, Chief of Department;
  • Lifshits Galina Izrailevna, MD, DM, Professor, Chief of Laboratory;
  • Sychev Dmitriy Alekseevich, MD, DM, Professor, Corresponding Member of Russian Academy of Sciences, Chief of Chair

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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