Feasibility of a Microarray-Based Point-of-Care CYP2C19 Genotyping Test for Predicting Clopidogrel On-Treatment Platelet Reactivity

被引:15
作者
Chae, Hyojin [1 ,2 ]
Kim, Myungshin [1 ,2 ]
Koh, Yoon-Seok [3 ,4 ]
Hwang, Byung-Hee [5 ,6 ]
Kang, Min-Kyu [5 ,6 ]
Kim, Yonggoo [1 ,2 ]
Park, Hae-il [1 ,2 ]
Chang, Kiyuk [5 ,6 ]
机构
[1] Bucheon St Marys Hosp, Dept Lab Med, Gyeonggi Do 420717, Bucheon Si, South Korea
[2] Catholic Univ Korea, Coll Med, Catholic Lab, Dev & Evaluat Ctr, Seoul 137701, South Korea
[3] Uijeongbu St Marys Hosp, Ctr Cardiovasc, Uijongbu 480717, South Korea
[4] Uijeongbu St Marys Hosp, Div Cardiol, Uijongbu 480717, South Korea
[5] Seoul St Marys Hosp, Ctr Cardiovasc, Seoul 137701, South Korea
[6] Seoul St Marys Hosp, Div Cardiol, Seoul 137701, South Korea
关键词
D O I
10.1155/2013/154073
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Clopidogrel is a prodrug which is converted into active metabolite by cytochrome P450 isoenzyme, CYP2C19. Numerous polymorphisms of CYP2C19 are reported, and a strong link exists between loss-of-function (LOF) or gain-of-function polymorphisms, clopidogrel metabolism, and clinical outcome. Hence, a fully automated point-of-care CYP2C19 genotyping assay is more likely to bring personalized antiplatelet therapy into real practice. We assessed the feasibility of the Verigene 2C19/CBS Nucleic Acid Test, a fully automated microarray-based assay, compared to bidirectional sequencing, and performed VerifyNow P2Y12 assay to evaluate the effect of CYP2C19 polymorphisms on on-treatment platelet reactivity in 57 Korean patients treated with clopidogrel after percutaneous coronary intervention. The Verigene 2C19/CBS assay identified *2, *3, and *17 polymorphisms with 100% concordance to bidirectional sequencing in 180 minutes with little hands-on time. Patients were classified into 4 groups: extensive (*1/*1; n = 12, 21.1%), intermediate (*1/*2, *1/*3; n = 33, 57.9%), poor (*2/*2, *2/*3, and *3/*3; n = 11, 19.3%), and ultrarapidmetabolizers (*1/*17; n = 1, 1.8%). The prevalence of the CYP2C19 *2, *3, and *17 alleles was 36.0%, 12.3%, and 0.9%. Platelet reactivity showed gene dose response according to the number of CYP2C19 LOF allele. In conclusion, the Verigene 2C19/CBS assay gave accurate CYP2C19 genotype results which were in well match with the differing on-treatment platelet reactivity.
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页数:5
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