|
|
|
| The relationship between CYP2C19 genetic polymorphism and Clopidogrel antiplatelet |
| DING Yasuo YIN Chun GAO Guangzhong LU Jun ZHANG Qin SUN Bing▲ |
| Department of Neurosurgery, Jiangsu Taizhou People′s Hospital of Nantong University, Jiangsu Province, Taizhou 225300, China |
|
|
|
Abstract Objective To explore the relationship between CYP2C19 Genetic Polymorphism and Clopidogrel in antiplatelet. Methods A total of 63 wide-necked intracranial aneurysm patients after stent-assist coiling embolization in the Neurosurgery Department of Jiangsu Taizhou People's Hospital of Nantong University were included in the study who took Clopidogrel (75 mg/d) and Aspirin (100 mg/d) orally. Gene chip kits were applied to test CYP2C19 gene types. In this research, six gene sub-types were tested（CYP2C19＊1/＊1 (636GG, 681GG), CYP2C19＊1/＊2 (636GG, 681GA), CYP2C19＊2/＊2 (636GG, 681AA), CYP2C19＊1/＊3 (636GA, 681GG), CYP2C19＊2/＊3 (636GA, 681GA), CYP2C19＊3/＊3 (636AA, 681GG). And they were divided into three subgroups based on the metabolic rate. CYP2C19＊1/＊1 (636GG, 681GG) was in the rapid subgroup. CYP2C19＊1/＊2 (636GG, 681GA) and CYP2C19＊1/＊3 (636GA, 681GG) were in the moderate subgroup. CYP2C19＊2/＊2 (636GG, 681AA), CYP2C19＊2/＊3 (636GA, 681GA) and CYP2C19＊3/＊3 (636AA, 681GG) were in the slow subgroup. Thrombelastograms were used to test the inhibition rate of platelet. Results CYP2C19＊1/＊1 and CYP2C19＊1/＊2 were the main gene sub-types, occupied 63.5% and 19.0% separately. There were 40 cases in rapid subgroup（63.5%), 12 cases in moderate subgroup (19.0%) and 11 cases in slow subgroup (17.5%). There was no statistical difference in the inhibition rate of ADP between rapid subgroup and slow subgroup (P > 0.05). Conclusion It is of little significance to adjust the amount of Clopidogrel in patients with wide-necked aneurysm stent after detecting genetype. Other indicators are needed to monitor the inhibition of plateles.
|
|
|
|
|
|
[1] Zhong X，Tong X，Ju Y，et al. Interpersonal factors in the pharmacokinetics and pharmacodynamics of voriconazole：are CYP2C19 genotypes enough for us to make a clinical decision? [J]. Curr Drug Metab，2017：56-59.
[2] Xi Z，Fang F，Wang J，et al. CYP2C19 genotype and adverse cardiovascular outcomes after stent implantation in clopidogrel-treated Asian populations：a systematic review and meta-analysis [J]. Platelets，2017（127）：1-12.
[3] Zhuo ZL，Xian HP，Long Y，et al. Association between CYP2C19 and ABCB1 polymorphisms and clopidogrel resistance in clopidogrel-treated Chinese patients [J]. Anatol J Cardiol，2018，19（2）：123-128.
[4] Guirgis M，Thompson P，Jansen S. Review of aspirin and clopidogrel resistance in peripheral arterial disease [J]. J Vasc Surg，2017，66（5）：1576-1586.
[5] Zeb I，Krim N，Bella J. Role of CYP2C19 genotype testing in clinical use of clopidogrel：is it really useful ? [J]. Expert Rev Cardiovasc Ther，2018，16（5）：369-377.
[6] Kim KA，Park PW，Hong SJ，et al. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel：a possible mechanism for clopidogrel resistance [J]. Clin Pharmacol Ther，2008，84（2）：236-242.
[7] Wang XQ，Shen CL，Wang BN，et al. Genetic polymorphisms of CYP2C19 2 and ABCB1 C3435T affect the pharmacokinetic and pharmacodynamic responses to clopidogrel in 401 patients with acute coronary syndrome [J]. Gene，2015，558（2）：200-207.
[8] Liu J，Nie XY，Zhang Y，et al. CYP2C19*2 and other allelic variants affecting platelet response to Clopidogrel tested by thrombelastography in patients with acute coronary syndrome [J]. Chin Med J （Engl），2015，128（16）：2183-2188.
[9] Lin XB，Li ZW，Yan M，et al. Population pharmacokinetics of Voriconazole and CYP2C19 polymorphisms for optimizing dosing regimens in renal transplant recipients [J]. Br J Clin Pharmacol，2018，84（7）：46-49.
[10] Hariharan S，Southworth MR，Madabushi R. Clopidogrel，CYP2C19 and proton pump inhibitors：what we know and what it means [J]. J Clin Pharmacol，2014，54（8）：884-888.
[11] Tang XF，Han YL，Zhang JH，et al. CYP2C19 genotyping combined with on-clopidogrel platelet reactivity in predicting major adverse cardiovascular events in Chinese patients with percutaneous coronary intervention [J]. Thromb Res，2016，147（5）：108-114.
[12] Xiao ZS，Goldstein JA，Xie HG，et al. Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele [J]. J Pharmacol Exp Ther，1997，281（1）：604-609.
[13] Mohammad Fic AM，Al-Allawi NA. CYP2C19 genotype is an independent predictor of adverse cardiovascular outcome in Iraqi patients on Clopidogrel post percutaneous coronary intervention [J]. J Cardiovasc Pharmacol，2018，37（7）：139-143.
[14] Lee CR，Sriramoju VB，Cervantes A，et al. Clinical outcomes and sustainability of using CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention [J]. Circ Genom Precis Med，2018，11（4）：e002069.
[15] Simon T，Verstuyft C，Mary-Krause M，et al. Genetic determinants of response to clopidogrel and cardiovascular events [J]. N Engl J Med，2009，360（4）：363-375.
[16] Chen K，Zhang R，Liu H，et al. Impact of the CYP2C19 gene polymorphism on Clopidogrel personalized drug regimen and the clinical outcomes [J]. Clin Lab，2016，62（9）：1773-1780.
[17] Rodriguez-Gonzalez F，Martinez-Quintana E，Saavedra P，et al. CYP2C19 or CYP3A5 genotyping does not predict clinical response to Clopidogrel [J]. J Clin Pharmacol，2018， 18（4）：198-202.
[18] Tomek A，Mat'oska V，Frydmanova A，et al. Impact of CYP2C19 polymorphisms on clinical outcomes and antiplatelet potency of Clopidogrel in caucasian poststroke survivors [J]. Am J Ther，2018，25（2）：e202-e212.
[19] Kiss AF，Vasko D，Deri MT，et al. Combination of CYP2C19 genotype with non-genetic factors evoking phenoconversion improves phenotype prediction [J]. Pharmacol Rep，2017，70（3）：525-532.
[20] Wu Y，Zhou Y，Pan Y，et al. Impact of CYP2C19 polymorphism in prognosis of minor stroke or TIA patients with declined eGFR on dual antiplatelet therapy：CHANCE substudy [J]. Pharmacogenomics J，2018，11（2）：45-49. |
|
|
|
