The Cytochrome P450 2C19 Polymorphism Associated with Major Adverse Cardiovascular Events Risk in Kazak Patients Undergoing Percutaneous Coronary Intervention and Receiving Clopidogrel

Page: [196 - 204] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: Clopidogrel activity is influenced by cytochrome P450 (CYP450). CYP2C19 polymorphisms vary by ethnicity and region.

Objective: The aim of the study is to assess the effect of genetic polymorphisms in CYP2C19*2 and *3 and clinical and demographic factors on major adverse cardiovascular events (MACE) in Kazak patients following percutaneous coronary intervention (PCI).

Methods: 397 patients with PCI treated with clopidogrel and aspirin for at least 12 months were enrolled and outcomes within 1 year were recorded. Approximately 2 ml of peripheral venous blood samples were used for genotype detection. Multivariable logistic regression analyses were performed to identify factors associated with MACE.

Results: 95 patients (23.9%) suffered MACE during the period. Logistic regression analysis revealed CYP2C19*2 carriers (odds ratio [OR]: 2.431, 95% [confidence interval] CI: 1.136- 5.275, P = 0.027) and poor metabolizers (OR: 2.128, 95% CI: 0.899-4.82, P = 0.043) to be significantly associated with MACE.

Conclusion: The CYP2C19*2 allele variants and poor metabolizers were found to be associated with MACE in a clopidogrel-treated Kazak population with acute coronary syndrome following PCI.

Keywords: CYP2C19, Clopidogrel, percutaneous coronary intervention, Kazak, PCI, Major Adverse Cardiovascular Events (MACE).

Graphical Abstract

[1]
Levine, G.N.; Bates, E.R.; Bittl, J.A.; Brindis, R.G.; Fihn, S.D.; Fleisher, L.A.; Granger, C.B.; Lange, R.A.; Mack, M.J.; Mauri, L.; Mehran, R.; Mukherjee, D.; Newby, L.K.; O’Gara, P.T.; Sabatine, M.S.; Smith, P.K.; Smith, S.C., Jr 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the american college of cardiology/american heart association task force on clinical practice guidelines: an update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention, 2011 ACCF/AHA guideline for coronary artery bypass graft surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease, 2013 ACCF/AHA guideline for the management of st-elevation myocardial infarction, 2014 AHA/ACC guideline for the management of patients with non-st-elevation acute coronary syndromes, and 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery. Circulation, 2016, 134(10), e123-e155.
[PMID: 27026020]
[2]
Pereira, N.L.; Rihal, C.S.; So, D.Y.F.; Rosenberg, Y.; Lennon, R.J.; Mathew, V.; Goodman, S.G.; Weinshilboum, R.M.; Wang, L.; Baudhuin, L.M.; Lerman, A.; Hasan, A.; Iturriaga, E.; Fu, Y.P.; Geller, N.; Bailey, K.; Farkouh, M.E. Clopidogrel pharmacogenetics. Circ. Cardiovasc. Interv., 2019, 12(4), e007811.
[http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.007811] [PMID: 30998396]
[3]
Tang, X.F.; Han, Y.L.; Zhang, J.H.; Wang, J.; Yao, Y.; He, C.; Xu, B.; Gao, Z.; Qiao, S.B.; Chen, J.; Wu, Y.; Chen, J.L.; Gao, R.L.; Yang, Y.J.; Yuan, J.Q. CYP2C19 genotyping combined with on-clopidogrel platelet reactivity in predicting major adverse cardiovascular events in Chinese patients with percutaneous coronary intervention. Thromb. Res., 2016, 147, 108-114.
[http://dx.doi.org/10.1016/j.thromres.2016.10.008] [PMID: 27728892]
[4]
Sofi, F.; Giusti, B.; Marcucci, R.; Gori, A.M.; Abbate, R.; Gensini, G.F. Cytochrome P450 2C19*2 polymorphism and cardiovascular recurrences in patients taking clopidogrel: A meta-analysis. Pharmacogenomics J., 2011, 11(3), 199-206.
[http://dx.doi.org/10.1038/tpj.2010.21] [PMID: 20351750]
[5]
Giusti, B.; Gori, A.M.; Marcucci, R.; Saracini, C.; Vestrini, A.; Abbate, R. Determinants to optimize response to clopidogrel in acute coronary syndrome. Pharm. Genomics Pers. Med., 2010, 3, 33-50.
[http://dx.doi.org/10.2147/PGPM.S5056] [PMID: 23226041]
[6]
Simon, T.; Verstuyft, C.; Mary-Krause, M.; Quteineh, L.; Drouet, E.; Méneveau, N.; Steg, P.G.; Ferrières, J.; Danchin, N.; Becquemont, L. Genetic determinants of response to clopidogrel and cardiovascular events. N. Engl. J. Med., 2009, 360(4), 363-375.
[http://dx.doi.org/10.1056/NEJMoa0808227] [PMID: 19106083]
[7]
Wang, T.; Zhao, T.; Bao, S.; Jia, L.; Feng, J.; Yu, A.; Sun, L.; Guo, X.; Li, H.; Yu, L. CYP2C19, PON1, and ABCB1 gene polymorphisms in Han and Uygur populations with coronary artery disease in Northwestern Xinjiang, China, from 2014 through 2019. Medicine (Baltimore), 2020, 99(29), e20582.
[http://dx.doi.org/10.1097/MD.0000000000020582] [PMID: 32702814]
[8]
Wang, T.; Li, H.; Wang, F.; Sun, L.; Yu, L. The effects of polymorphisms in CYP2C19, ATP-binding cassette transporter B1, and paraoxonase-1 on clopidogrel treatment of Uygur patients following percutaneous coronary intervention. Eur. J. Clin. Pharmacol., 2021, 77(11), 1679-1686.
[http://dx.doi.org/10.1007/s00228-021-03176-z] [PMID: 34164723]
[9]
Kim, H.S.; Lim, Y.; Oh, M.; Ghim, J.L.; Kim, E.Y.; Kim, D.H.; Shin, J.G. The pharmacokinetic and pharmacodynamic interaction of clopidogrel and cilostazol in relation to CYP2C19 and CYP3A5 genotypes. Br. J. Clin. Pharmacol., 2016, 81(2), 301-312.
[http://dx.doi.org/10.1111/bcp.12794] [PMID: 26426352]
[10]
Sibbing, D.; Stegherr, J.; Latz, W.; Koch, W.; Mehilli, J.; Dörrler, K.; Morath, T.; Schömig, A.; Kastrati, A.; von Beckerath, N. Cytochrome P450 2C19 loss-of-function polymorphism and stent thrombosis following percutaneous coronary intervention. Eur. Heart J., 2009, 30(8), 916-922.
[http://dx.doi.org/10.1093/eurheartj/ehp041] [PMID: 19193675]
[11]
Ferri, N.; Corsini, A.; Bellosta, S. Pharmacology of the new P2Y12 receptor inhibitors: Insights on pharmacokinetic and pharmacodynamic properties. Drugs, 2013, 73(15), 1681-1709.
[http://dx.doi.org/10.1007/s40265-013-0126-z] [PMID: 24114622]
[12]
Lin, R.; Zhang, L.; Zhang, P.; Zhou, L.; Liu, T.; Li, Y.; Zhang, W.; Wang, W.; Zhang, J. Influence of CYP2C19 loss-of-function variants on the metabolism of clopidogrel in patients from north-western China. J. Clin. Pharm. Ther., 2015, 40(3), 308-314.
[http://dx.doi.org/10.1111/jcpt.12254] [PMID: 25810245]
[13]
Yin, T.; Miyata, T. Pharmacogenomics of clopidogrel: Evidence and perspectives. Thromb. Res., 2011, 128(4), 307-316.
[http://dx.doi.org/10.1016/j.thromres.2011.04.010] [PMID: 21592545]
[14]
Yu, L.; Wang, T.; Bai, H.; Zhu, W.; Li, Y.; Wu, J.; Liu, W.; Sun, L.; Yu, A.; Li, H. Association between cytochrome P450 2C19 polymorphism and clinical outcomes in clopidogrel-treated Uygur population with acute coronary syndrome: A retrospective study. BMC Cardiovasc. Disord., 2021, 21(1), 391.
[http://dx.doi.org/10.1186/s12872-021-02201-4] [PMID: 34384383]
[15]
Dehbozorgi, M.; Kamalidehghan, B.; Hosseini, I.; Dehghanfard, Z.; Sangtarash, M.H.; Firoozi, M.; Ahmadipour, F.; Meng, G.Y.; Houshmand, M. Prevalence of the CYP2C19*2 (681 G>A), *3 (636 G>A) and *17 (806 C>T) alleles among an Iranian population of different ethnicities. Mol. Med. Rep., 2018, 17(3), 4195-4202.
[http://dx.doi.org/10.3892/mmr.2018.8377] [PMID: 29328413]
[16]
Scott, S.A.; Sangkuhl, K.; Stein, C.M.; Hulot, J.S.; Mega, J.L.; Roden, D.M.; Klein, T.E.; Sabatine, M.S.; Johnson, J.A.; Shuldiner, A.R. Clinical pharmacogenetics implementation consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin. Pharmacol. Ther., 2013, 94(3), 317-323.
[http://dx.doi.org/10.1038/clpt.2013.105] [PMID: 23698643]
[17]
Kim, H.; Kim, Y.; Koh, Y.S.; Lee, H.K.; Chae, H.; Jekarl, D.W.; Lee, J.M.; Shin, W.S.; Kim, T.H. Evaluation of the INNOVANCE PFA P2Y assay and its association with CYP2C19 genotypes. Platelets, 2015, 26(2), 148-153.
[http://dx.doi.org/10.3109/09537104.2014.889291] [PMID: 24617511]
[18]
Lewis, J.P.; Stephens, S.H.; Horenstein, R.B.; O’Connell, J.R.; Ryan, K.; Peer, C.J.; Figg, W.D.; Spencer, S.D.; Pacanowski, M.A.; Mitchell, B.D.; Shuldiner, A.R. The CYP2C19*17 variant is not independently associated with clopidogrel response. J. Thromb. Haemost., 2013, 11(9), 1640-1646.
[http://dx.doi.org/10.1111/jth.12342] [PMID: 23809542]
[19]
Park, J.J.; Park, K.W.; Kang, J.; Jeon, K.H.; Kang, S.H.; Ahn, H.S.; Han, J.K.; Koh, J.S.; Lee, S.E.; Yang, H.M.; Lee, H.Y.; Kang, H.J.; Koo, B.K.; Oh, B.H.; Park, Y.B.; Kim, H.S. Genetic determinants of clopidogrel responsiveness in Koreans treated with drug-eluting stents. Int. J. Cardiol., 2013, 163(1), 79-86.
[http://dx.doi.org/10.1016/j.ijcard.2012.09.075] [PMID: 23260377]
[20]
Swen, J.J.; Nijenhuis, M.; de Boer, A.; Grandia, L.; Maitland-van der Zee, A.H.; Mulder, H.; Rongen, G.A.; van Schaik, R.H.; Schalekamp, T.; Touw, D.J.; van der Weide, J.; Wilffert, B.; Deneer, V.H.; Guchelaar, H.J. Pharmacogenetics: From bench to byte--an update of guidelines. Clin. Pharmacol. Ther., 2011, 89(5), 662-673.
[http://dx.doi.org/10.1038/clpt.2011.34] [PMID: 21412232]
[21]
Kim, H.S.; Cho, D.Y.; Park, B.M.; Bae, S.K.; Yoon, Y.J.; Oh, M.; Ghim, J.L.; Kim, E.Y.; Kim, D.H.; Shin, J.G. The effect of CYP2C19 genotype on the time course of platelet aggregation inhibition after clopidogrel administration. J. Clin. Pharmacol., 2014, 54(8), 850-857.
[http://dx.doi.org/10.1002/jcph.225] [PMID: 24214141]
[22]
Song, B.L.; Wan, M.; Tang, D.; Sun, C.; Zhu, Y.B.; Linda, N.; Fan, H.W.; Zou, J.J. Effects of CYP2C19 genetic polymorphisms on the pharmacokinetic and pharmacodynamic properties of clopidogrel and its active metabolite in healthy chinese subjects. Clin. Ther., 2018, 40(7), 1170-1178.
[http://dx.doi.org/10.1016/j.clinthera.2018.06.001] [PMID: 30017169]
[23]
Li, X.; Wang, Z.; Wang, Q.; Xu, Q.; Lv, Q. Clopidogrel-associated genetic variants on inhibition of platelet activity and clinical outcome for acute coronary syndrome patients. Basic Clin. Pharmacol. Toxicol., 2019, 124(1), 84-93.
[http://dx.doi.org/10.1111/bcpt.13110] [PMID: 30098132]
[24]
Wang, T.; Sun, L.; Xu, L.; Zhao, T.; Feng, J.; Yu, L.; Wu, J.; Li, H. Prevalence of dyslipidemia and gene polymorphisms of ABCB1 and SLCO1B1 in Han, Uygur, Kazak, Hui, Tatar, Kirgiz, and Sibe populations with coronary heart disease in Xinjiang, China. Lipids Health Dis., 2021, 20(1), 116.
[http://dx.doi.org/10.1186/s12944-021-01544-3] [PMID: 34563206]
[25]
Brunner, F.J.; Waldeyer, C.; Ojeda, F.; Salomaa, V.; Kee, F.; Sans, S.; Thorand, B.; Giampaoli, S.; Brambilla, P.; Tunstall-Pedoe, H.; Moitry, M.; Iacoviello, L.; Veronesi, G.; Grassi, G.; Mathiesen, E.B.; Söderberg, S.; Linneberg, A.; Brenner, H.; Amouyel, P.; Ferrières, J.; Tamosiunas, A.; Nikitin, Y.P.; Drygas, W.; Melander, O.; Jöckel, K.H.; Leistner, D.M.; Shaw, J.E.; Panagiotakos, D.B.; Simons, L.A.; Kavousi, M.; Vasan, R.S.; Dullaart, R.P.F.; Wannamethee, S.G.; Risérus, U.; Shea, S.; de Lemos, J.A.; Omland, T.; Kuulasmaa, K.; Landmesser, U.; Blankenberg, S.; Zeller, T.; Kontto, J.; Männistö, S.; Metspalu, A.; Lackner, K.; Wild, P.; Peters, A.; Meisinger, C.; Donfrancesco, C.; Signorini, S.G.; Alver, M.; Woodward, M.; Gianfagna, F.; Costanzo, S.; Wilsgaard, T.; Eliasson, M.; Jørgensen, T.; Völzke, H.; Dörr, M.; Nauck, M.; Schöttker, B.; Lorenz, T.; Makarova, N.; Twerenbold, R.; Dallongeville, J.; Dobson, A.; Malyutina, S.; Pajak, A.; Engström, G.; Bobak, M.; Schmidt, B.; Jääskeläinen, T.; Niiranen, T.; Jousilahti, P.; Giles, G.; Hodge, A.; Klotsche, J.; Magliano, D.J.; Lyngbakken, M.N.; Hveem, K.; Pitsavos, C.; Benjamin, E.J.; Bakker, S.J.L.; Whincup, P.; Ikram, M.K.; Ingelsson, M.; Koenig, W. Application of non-HDL cholesterol for population-based cardiovascular risk stratification: Results from the multinational cardiovascular risk consortium. Lancet, 2019, 394(10215), 2173-2183.
[http://dx.doi.org/10.1016/S0140-6736(19)32519-X] [PMID: 31810609]
[26]
Yan, W.; Yang, X.; Zheng, Y.; Ge, D.; Zhang, Y.; Shan, Z.; Simu, H.; Sukerobai, M.; Wang, R. The metabolic syndrome in Uygur and Kazak populations. Diabetes Care, 2005, 28(10), 2554-2555.
[http://dx.doi.org/10.2337/diacare.28.10.2554] [PMID: 16186300]
[27]
Tao, Y.; Mao, X.; Xie, Z.; Ran, X.; Liu, X.; Wang, Y.; Luo, X.; Hu, M.; Gen, W.; Zhang, M.; Wang, T.; Ren, J.; Wufuer, H.; Li, L. The prevalence of type 2 diabetes and hypertension in Uygur and Kazak populations. Cardiovasc. Toxicol., 2008, 8(4), 155-159.
[http://dx.doi.org/10.1007/s12012-008-9024-0] [PMID: 18777166]
[28]
Gu, D.; Reynolds, K.; Wu, X.; Chen, J.; Duan, X.; Reynolds, R.F.; Whelton, P.K.; He, J. Prevalence of the metabolic syndrome and overweight among adults in China. Lancet, 2005, 365(9468), 1398-1405.
[http://dx.doi.org/10.1016/S0140-6736(05)66375-1] [PMID: 15836888]
[29]
Nguyen, H.N.; Fujiyoshi, A.; Abbott, R.D.; Miura, K. Epidemiology of cardiovascular risk factors in Asian countries. Circ. J., 2013, 77(12), 2851-2859.
[http://dx.doi.org/10.1253/circj.CJ-13-1292] [PMID: 24240435]
[30]
Yusuf, S.; Hawken, S.; Ounpuu, S.; Bautista, L.; Franzosi, M.G.; Commerford, P.; Lang, C.C.; Rumboldt, Z.; Onen, C.L.; Lisheng, L.; Tanomsup, S.; Wangai, P., Jr; Razak, F.; Sharma, A.M.; Anand, S.S. Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: A case-control study. Lancet, 2005, 366(9497), 1640-1649.
[http://dx.doi.org/10.1016/S0140-6736(05)67663-5] [PMID: 16271645]
[31]
Crimi, G.; Somaschini, A.; Cattaneo, M.; Angiolillo, D.J.; Piscione, F.; Palmerini, T.; De Servi, S. Cigarette smoking reduces platelet reactivity independently of clopidogrel treatment in patients with non-ST elevation acute coronary syndromes. Platelets, 2018, 29(3), 309-311.
[http://dx.doi.org/10.1080/09537104.2017.1394452] [PMID: 29206072]
[32]
Grenfell, R.D. National guidelines for the management of absolute cardiovascular disease risk. Med. J. Aust., 2013, 199(4), 244.
[http://dx.doi.org/10.5694/mja13.10968] [PMID: 23984779]
[33]
Ma, L.; Yuan, Y.; Li, J.; Yu, C.; Zhao, J. Distribution of CYP2C19, ABCB1 and PON1 polymorphisms in Chinese Han, Hui, Uygur and Kazak patients with coronary atherosclerotic heart disease. Int. J. Immunogenet., 2020, 47(6), 539-545.
[http://dx.doi.org/10.1111/iji.12511] [PMID: 32862511]