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

Chae H, Kim M, Koh YS, Hwang BH, Kang MK, Kim Y, Park HI, Chang K.

Source

Department of Laboratory Medicine, Bucheon St. Mary's Hospital, 2 Sosa-dong, Wonmi-gu, Gyeonggi-do, Bucheon-si 420-717, Republic of Korea ; Catholic Laboratory Development and Evaluation Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.

Abstract

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 ultrarapid metabolizers (∗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.