Acute coronary syndrome (ACS) carries a high mortality in Uygur populations. Percutaneous coronary intervention (PCI) is a safe treatment for patients with ACS. Clopidogrel reduces the risk for recurrent cardiovascular events after PCI; however, its activity is influenced by cytochrome P450 (CYP450), ATP-binding cassette transporter B1 (ABCB1), and paraoxonase-1 (PON1).
To assess the effects of genetic polymorphisms CYP2C19*2, *3, *17, ABCB1 C3435T, and PON1 Q192R along with clinical and demographic factors on variations in responses in Uygur patients following PCI.
We enrolled 281 patients with PCI who were treated with clopidogrel and aspirin for at least 12 months and recorded major adverse cardiovascular events (MACE) or bleeding within 1 year. Approximately, 2 mL of peripheral venous blood samples were used for genotype detection. Binary logistic regression with likelihood ratio forward stepwise analysis and redundancy analysis were carried out to identify factors associated with MACE. We analyzed risk factors including age, body mass index, smoking, hypertension, dyslipidemia, gender, alcohol consumption, diabetes mellitus, carriers of ABCB1 C3435T T allele, carriers of PON1 Q192R A allele, metabolizer phenotype of CYP2C19, number of targeted vessels, and number of stents.
The CYP2C19 IMs (OR 3.546, 95% CI 1.972–6.375, P = 0.001), CYP2C19 PMs (OR 7.038, 95% CI 1.658–29.880, P = 0.008), and number of targeted vessels (OR 2.033, 95% CI 1.078–3.648, P = 0.026) were significantly associated with MACE.
The CYP2C19 IMs, PMs, and the number of targeted vessels are essential factors associated with MACE risk in dual clopidogrel-treated Uygur population with ACS following PCI. These data provide valuable insights into the genetic polymorphisms affecting clopidogrel response among minority groups in China.
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Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA et al (2016) 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 134:e123–e155
Pereira NL, Rihal CS, So DYF, Rosenberg Y, Lennon RJ (2019) Clopidogrel pharmacogenetics. Circ Cardiovasc Interv 12(4):e007811
Sofi F, Giusti B, Marcucci R, Gori AM, Abbate R, Gensini GF (2011) Cytochrome P450 2C19*2 polymorphism and cardiovascular recurrences in patients taking clopidogrel: a meta-analysis. Pharmacogenomics J 11:199–206
Giusti B, Gori AM, Marcucci R, Saracini C, Vestrini A et al (2010) Determinants to optimize response to clopidogrel in acute coronary syndrome. Pharmgenomics Pers Med 3:33–50
Mega JL, Simon T, Collet JP, Anderson JL, Antman EM et al (2010) Reduced-function cyp2c19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for pci: a meta-analysis. JAMA 304:1821–1830
Wang Y, Zhao X, Lin J, Li H, Johnston SC, Lin Y et al (2016) Association between CYP2C19 loss-of-function allele status and efficacy of clopidogrel for risk reduction among patients with minor stroke or transient ischemic attack. JAMA 316(1):70–78
Simon T, Verstuyft C, Mary-Krause M et al (2009) Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 360:363e75
Wang T, Zhao T, Bao S, Jia L, Feng J et al (2020) 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) 99(29): e20582
Mega JL, Close SL, Wiviott SD et al (2010) Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis. Lancet 376(9749):1312–1319
Marchini JF, Pinto MR, Novaes GC et al (2017) Decreased platelet responsiveness to clopidogrel correlates with CYP2C19 and PON1 polymorphisms in atherosclerotic patients. Braz J Med Biol Res 50:e5660
Chen QJ, Lai HM, Chen BD et al (2016) Appropriate LDL-C-to-HDL-C ratio cutoffs for categorization of cardiovascular disease risk factors among Uygur adults in Xinjiang, China. Int J Environ Res Public Health 13:235
R Core Team (2020) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/
Oksanen J, Blanchet FG, Friendly M, Kindt R, Legendre P, McGlinn D et al (2017) Vegan: community ecology package. R Package Version 2.4–3. Vienna, AU: R Core Development Team. Available at: https://CRAN.R-project.org/package=vegan
Wickham H (2016) ggplot2: elegant graphics for data analysis. Springer-Verlag, New York
Yusuf S, Hawken S, Ôunpuu S, Bautista L, Franzosi MG, Commerford P et al (2005) Obesity and the risk of myocardial infarction in 27 000 participants from 52 countries: a case-control study. Lancet 366(9497):1640–1649
Dhingra R, Vasan RS (2012) Age as a risk factor. Med Clin NorthAm 96(1):87–91
Bucerius J, Duivenvoorden R, Mani V et al (2011) Prevalence and risk factors of carotid vessel wall inflammation in coronary artery disease patients: FDG-PET and CT imaging study. JACC Cardiovasc Imaging 4(11):1195–1205
Crimi G, Somaschini A, Cattaneo M, Angiolillo DJ, Piscione F et al (2018) Cigarette smoking reduces platelet reactivity independently of clopidogrel treatment in patients with non-ST elevation acute coronary syndromes. Platelets 29(3):309–311
Nguyen HN, Fujiyoshi A, Abbott RD, Miura K (2013) Epidemiology of cardiovascular risk factors in Asian countries. Circ J 77(12):2851–2859
Lin R, Zhang L, Zhang P et al (2015) Influence of CYP2C19 loss-of-function variants on the metabolism of clopidogrel in patients from north-western China. J Clin Pharm Ther 40:308–314
Lewis JP, Stephens SH, Horenstein RB et al (2013) The CYP2C19 ∗ 17 variant is not independently associated with clopidogrel response. J Thromb Haemost 11:1640–1646
Park JJ, Park KW, Kang J et al (2013) Genetic determinants of clopidogrel responsiveness in Koreans treated with drug-eluting stents. Int J Cardiol 163:79–86
Swen JJ, Nijenhuis M, de Boer A et al (2011) Pharmacogenetics: from bench to byte-an update of guidelines. Clin Pharmacol Ther 89:662–673
Stokanovic D, Nikolic VN, Konstantinovic SS, Zvezdanovic JB, Lilic J, Apostolovic SR et al (2016) P-Glycoprotein polymorphism C3435T is associated with dose-adjusted clopidogrel and 2-oxo-clopidogrel concentration. Pharmacology 97(3–4):101–106
Berinstein E, Levy A (2017) Recent developments and future directions for the use of pharmacogenomics in cardiovascular disease treatments. Expert Opin Drug Metab Toxicol 13(9):973–983
Tang X-F, Han Y-L, Zhang J-H, Wang J, Yao Yi et al (2016) CYP2C19 genotyping combined with on-clopidogrel platelet reactivity in predicting major adverse cardiovascular events in Chinese patients with percutaneous coronary intervention. Thromb Res 147:108–114
Li X, Wang Zi, Wang Q, Qing Xu, Lv Q (2019) Clopidogrel-associated genetic variants on inhibition of platelet activity and clinical outcome for acute coronary syndrome patients. Basic Clin Pharmacol Toxicol 124(1):84–93
Sibbing D, Koch W, Gebhard D et al (2010) Cytochrome 2C19 ∗ 17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation 121:512–518
Park DW, Kwon O, Jang JS, Yun SC, Park H et al (2019) Duk-Woo Park, Clinically significant bleeding with ticagrelor versus clopidogrel in Korean patients with acute coronary syndromes intended for invasive management a randomized clinical trial. Circulation 140(23):1865–1877
Grenfell RD (2013) Guidelines for the management of absolute cardiovascular disease risk. Med J Aust 199–244
The authors disclosed receipt of the following financial support for the research and/or publication of this article: This work was supported by 1.General program of Natural Science Foundation of Xinjiang Uygur Autonomous Region, Project No. 2018D01C108.; 2. Tianshan District Science and Technology Foundation of Urumqi, Xinjiang, Project No. T2017-07.
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The authors declare no competing interests.
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Wang, T., Li, H., Wang, F. et al. 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). https://doi.org/10.1007/s00228-021-03176-z
- Percutaneous coronary intervention